Block 34 Week 6 Flashcards
signs and symptoms of anemia?
- General fatigue
- Weakness
- Dyspnea on exertion
- Pallor
vegan diet?
B12 def - can only be obtained from animal sources
alcoholism?
B9 (folate) def
autoimmune conditions?
- autoimmune conditions like lupus or lymphoma can predispose to autoimmune hemolytic anemia
features that would indicate IDA caused by bleeding?
- melena, epistaxis, hematochezia, hematemesis, or menorrhagia indicates bleeding.
features indicating haemolysis?
- Jaundice and dark urine, in the absence of liver disease, suggest hemolysis.
Diffuse severe bone or chest pain may suggest?
sickle cell disease,
stocking-glove parasthesia?
may suggestvitamin B12 deficiency.
jaundice may suggest
acute bleeding
splenomegaly?
may occur with hemolysis, a hemoglobinopathy, connective tissue diseases, myeloproliferative disorders, infection, or cancer.
peripheral neuropathy suggests
B12 def
fever and murmus may suggest
infective endo
what are the microcytic anaemias?
- altered heme or globin synthesis
- iron deficiency
- thalassemia
- sideroblastic anemia
- lead poisoning
- anemia of CD - MCV is microcytic or borderline microcytic - but more commonly a normocytic anemia
what are the megaloblastic macrocytic anaemias?
- impaired DNA synthesis - B12, B9 deficiency,
- methotrexate
what are the normoblastic macrocyctic anaemias?
- alcohol use disorders
- chemo drugs like hydroxyurea or antifolate
- hypothyoridism
- liver disease
- pregnancy
what are the normocytic anaemuas?
- deficiency in EPO or inadequate resp to it
- haemorrhage
- anemia of CD
- CKD
- aplastic anemia
- acute blood loss
- haemolytic anemia
reticulocyte count?
- higher values indicate excessive production (reticulocytosis); in the presence of anemia, reticulocytosis suggests excessive RBC destruction.
- Low numbers in the presence of anemia indicate decreased RBC production.
general symptoms of anaemia?
- Dyspnoea
- Fatigue
- Headache
- Dizziness
- Syncope
- Confusion
- Palpitations
- Angina
underlying causes of anaemia - table
Signs of anaemia
- Bounding pulse
- Postural hypotension
- Tachycardia
- Conjunctival pallor
- shock
mneumonic for microcytic anaemia
- Fe
- thalassemia
- sideroblastic anemia
- chronic disease
IDA signs?
- Atrophic glossitis
- Angular Stomatitis
- Koilonychia
- Pica – craving non-food substances such as ice or dirt
- Restless leg syndrome
- Rarely, tachycardia and signs of heart failure
sideroblastic anaemia?
- group of disorders characterised by dysfunctional haemoglobin synthesis in the mitochondria.
- This leads to the formation of ring sideroblasts in the cytoplasm and microcytic cells secondary to the disease pathogenesis.
deficiency?
causes of sideroblactic anaemia?
- Causes include genetic enzyme deficiency, and environmental causes: vitamin B6 deficiency, lead poisoning and chronic alcoholism.
thalassemia?
- absence of one of the globin genes -> accumulation of the excess chain type in red blood cells which predisposes them to oxidative damage
- reduced hb synthesis -> microcytic anemia
pres of thalassemia?
- general anemia symptoms
- Due to the excessive haemolysis secondary to oxidative damage, jaundice may also be apparent.
- In beta thalassaemia major the bone marrow expands to compensate for the ineffective erythropoiesis leading to jaw and forehead expansion – ‘thalassaemia facies’.
- These individuals may also be prone to more infections.
examination for thalassemia?
may have hepatomegaly or splenomegaly.
There are some clinical features specific to haemolytic anaemias, including:
- Jaundice
- Splenomegaly
- Gallstones
- Aplastic crisis after parvovirus infection
what is elevated in haemolysiss?
- Bilirubin and LDH are elevated in a haemolysis picture due to increased cell breakdown.
- Reticulocytosis may be seen, which is the increase of the red blood cell progenitor, the reticulocyte, in the circulation.
- This occurs as the bone marrow attempts to compensate for the excessive RBC breakdown.
macrocytic anaemia mneumonic?
FAT RBC
- Foetus (pregnancy)
- Alcohol excess
- Thyroid (hypo)
- Reticulocytosis
- B12 and folate deficiency
- Chronic liver disease
perinicious anaemia?
- intrinsic factor normally secreted by parietal cells
- Pernicious anaemia occurs when this process is disrupted due to autoantibodies destroying the parietal cells or intrinsic factor itself.
neuropsychiatric features of b12 deficiency?
- when its long standing or severe
- neuro:
- peripheral neuropathy
- subacute degen of the cord
- focal demylination
- psych:
- depression
- personality change
- memory loss
where is folate abs?
- Normal absorption of folate occurs in the proximal part of the small intestines.
- Conditions that affect this area of the bowel, such as coeliac disease, can lead to deficiency.
when is folate def more common?
malnutrition and pregnancy
sideroblastic anaemia?
- enough iron is produced but can’t be carried into the hb
aplastic anaemia?
- bone marrow failure - body unable to make sufficient numbers of blood cells
- assoc w cancers
- deficiency of all typpes: red. white and platelets
b12 def blood film?
- Blood film reveals amegaloblastic anaemia +/- hypersegmented neutrophils.
Mx of B12 deficiency?
- B12 replacement - IM
- Importantly, in patients with co-existing folate deficiency, B12must be replaced first as folate replacement in this setting may precipitate neurological complications (e.g. subacute degeneration of the cord).
perinicious anaemia?
- B12 def from autoimmune destruction of gastric epithelium
- anti-parietal cell ab
- anti-IF ab
perinicious anaemia increases risk of?
- inc risk of gastric malignancy - upper GI endoscopy needed at diagnosis
Ix for perinicious anaemia?
- FBC
- peripheral blood smear
- serum vitamin B12 and folate levels
- testing for iF ab and parietal cell ab
- Schilling test for B12 def
- bone marrow aspiration and biopsy
symptoms of haemological malignancies?
- Fatigue
- weight loss
- fever and night sweats - esp lymphomas
- freq infections
- easy bruising and bleeding
- Swollen, painless lymph nodes in the neck, armpits, or groin are common in lymphomas and some leukemias.
signs of haem malignancies?
- splenomegaly or hepatomegaly may cause discomfort or pain in the upper abdomen.
- Bone Pain or Tenderness: Bone pain, particularly in the long bones or back, can occur due to the infiltration of cancer cells into the bone marrow.
- SOB - aneamia or lung involvement
- neurological symptoms if CNS involved
Referral should be arranged urgently using a suspected cancer pathway for an appointment within 2 weeks for:
- People aged over 60 years with iron deficiency anaemia.
- Women aged over 55 years withpostmenopausal bleeding.
- People who have a faecal immunochemical testing result of at least 10 micrograms of haemoglobin per gram of faeces.
- Urgent referral should be considered for people aged under 50 years with rectal bleeding.
When should a referral to GE be arranged?
- all men and post MP women w IDA unless they have overt non-gastrointestinalbleeding.
- All people aged 50 years or overwithmarked anaemia, or a significant family history of colorectal carcinoma, even if coeliac disease is found.
- Premenopausal women if they areaged under 50 yearsand have colonic symptoms, a strong family history (two affected first-degree relatives or just one first-degree relative affected before the age of 50 years) of gastrointestinal cancer, persistent iron deficiency anaemia despite treatment, or if they do not menstruate (for example following hysterectomy).
Ix for normochromic normocytic anaemia?
- FBC
- Peripheral blood smear - morphological abnormalities in red blood cells, white blood cells, and platelets. This can help identify specific etiologies such as hemolysis, bone marrow disorders, or other underlying conditions.
Iron studies?
- Serum Iron: Measure serum iron levels to assess iron status.
- Total Iron-Binding Capacity (TIBC): Evaluate TIBC to assess transferrin levels.
- Transferrin Saturation: Calculate transferrin saturation to assess iron utilization.
Additional tests for IDA?
- Serum Ferritin: Measure serum ferritin levels to assess iron stores.
- Renal Function Tests: Perform renal function tests, including serum creatinine and blood urea nitrogen (BUN), to assess kidney function.
- Liver Function Tests: Evaluate liver function with tests such as serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
- Inflammatory Markers: Measure inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to assess for underlying inflammation.
Ix for haemolytic anaemias?
- Reticulocyte Count: An elevated reticulocyte count indicates increased red blood cell production in response to hemolysis.
- Haptoglobin: Decreased levels of haptoglobin indicate hemolysis, as haptoglobin binds free hemoglobin in the bloodstream.
- Serum LDH: Elevated LDH levels are a marker of hemolysis, as LDH is released from damaged red blood cells.
Referral for haemolytic anaemia?
- Suspected or confirmed diagnosis of hemolytic anemia based on laboratory investigations and clinical assessment.
- Severe or life-threatening hemolytic anemia requiring urgent intervention or hospitalization.
- Hemolytic anemia refractory to initial treatment or associated with complications such as acute hemolysis, hemolytic crisis, or organ dysfunction.
- Presence of specific underlying conditions associated with hemolytic anemia that require specialized expertise for diagnosis and management, such as autoimmune hemolytic anemia, hereditary spherocytosis, sickle cell disease, thalassemia, or paroxysmal nocturnal hemoglobinuria (PNH).
inherited haemolytic anaemias?
- metabolic abn - G6PD deficiency which protects E from oxidative stress
- haemaglobin abn - sickle cell, thalassemia
- membrane abn - hereditary spherocytosis - results in premature removal by splenic macrophages
autoimmune mediated haemolytic anaemia?
- ab against the RBC
- e.g. autoimmune haemolytic anaemia (AIHA). It is characterised by either warm-reactive antibodies or cold haemagglutinins.
causes of non-immune mediated destruction?
- include mechanical distortion from abnormal surfaces (e.g. prosthetic heart valve),
- passing through abnormal intravascular fibrin strands (e.g. microangiopathic haemolytic anaemia),
- infections,
- drugs or an
- overactive spleen (e.g. hypersplenism).
- Fatigue
- Weakness
- Paraesthesia
- Dyspnoea
- Gastrointestinal symptoms(e.g. nausea, dyspepsia)
- Weight loss
signs of haemolytic anaemia?
- Atrophic glossitis
- Pallor
- Fever
- Splenomegaly
- Evidence of underlying disease
signs of haemolysis?
- Jaundice
- Abdominal pain(e.g. gallstones)
- Dark urine(e.g. haemoglobinuria secondary to intravascular haemolysis)
haemolytic screen?
- FBC(inc. reticulocyte count)
- Blood film
- LDH
- LFTs(bilirubin)
- Serum haptoglobin
- Additional tests
which type of anaemia does haemolytic anemia cause?
normocytic w raised reticulocyte count
inc reticulocytes in haem anaemia?
- The normal percentage of reticulocytes in the peripheral blood is 1-2%.
- In the absence of bone marrow disease, an increase in RBC destruction leads to the release of EPO, which stimulates the bone marrow to produce more erythrocytes, subsequently increasing the percentage or reticulocytes.
Typical erythrocyte morphologies associated with haemolysis may include:
- Spherocytes(e.g. hereditary spherocytosis)
- Schistocytes(e.g. microangiopathic haemolytic anaemia)
- Sickle cells(e.g. sickle cell disease)
Hereditary spherocytosis?
- most common inherited form of haemolysis
- usually transmitted in an autosomal dominant pattern
- characterised by mutations that lead to defects within the RBC membrane resulting in cytoskeleton instability.
Hereditary spherocytosis is assoc w?
- associated with a low haemoglobin concentration, raised reticulocyte count and spherocytes seen on blood film,
- which are smaller and denser erythryocytes that have a sphere shape as opposed to biconcave shape
- treatment typically involves splenectomy
GDP6 deficiency?
- X linked disorder
- can lead to haemolysis in presence of oxidative stressors
- avoidance of fava beans, types of henna and numerous drugs
drugs that can trigger haemolysis in GDP-6 def?
ciprofloxacin, sulfonylureas(e.g.,gliclazide
* sulfasalazine.
alloantibodies?
- Alloantibodiesare antibodies produced by one individual that will react with antigens of another individual of the same species. May be seen in haemolytic transfusion reactions and haemolytic disease of the newborn.
Autoantibodies?
- Autoantibodies, which are generated against components of the individuals own tissue, may be seen in AIHA. AIHA is further divided depending on the type of autoantibody present being ‘warm’ or ‘cold’.
Warm autoimmune haemolytic anaemia?
- ab reaction against erythrocytes at higher temps -> agglutination
- may be idiopathic, or assoc w immune dysfunction secondary to infection or malignancy
what can Warm AIHA be associated w?
- Warm AIHA may be associated with infections such as HIV and EBV, inflammatory disorders such as SLE, or malignancies such as chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma.
Cold AIHA?
- assoc w reactipn at lower T <32
- AIHA may be idiopathic or associated with:
- **lymphoma,
- Mycoplasma pneumoniaeinfection a
- infectious mononucleosis.
Non-immune mediated HE?
- Mechanical trauma- due to heart and large blood vessel pathology (e.g. prostheses).
- Microangiopathic haemolytic anaemia(e.g. HUS, TTP, DIC).
- Burns
- Infections
- Drugs & chemicals
- Hypersplenism
in which ppts should colonoscopy be avoided?
In patients with severe colitis, colonoscopy should be avoided due to the risk of perforation - a flexible sigmoidoscopy is preferred
mutation in hereditary non polyposis CRC
MSH2/MLH1 gene mutations are associated with hereditary non-polyposis colorectal carcinoma
mutation in FAP?
APC
biliary colic vs cholesystitis vs cholangitis?
Biliary colic: RUQ pain
Cholecystitis: RUQ pain + Fever
Cholangitis: RUQ pain + Fever + Jaundice
which drug can cause cholestasis?
co-amoxiclav
PPIs can cause…
hyponatreamia
what is allo-immunisation?
- allo-immunisation refers to the development of antibodies against red blood cell antigens that can potentially harm the fetus during pregnancy.
- Prevention measures in the UK focus on identifying and managing at-risk women
Measures of preventing allo-immunisation?
- antenatal screening
- RhD immunoprophylaxis
- testing for other ab
antenatal screening?
- Blood samples are tested to determine the woman’s blood group (ABO and RhD), as well as the presence of any irregular antibodies (e.g., anti-D, anti-Kell).
RhD immunoprophylaxis?
- RhD-negative women who are not sensitized to the RhD antigen are offered RhD immunoprophylaxis (anti-D immunoglobulin) to prevent sensitization during pregnancy and childbirth.
- Anti-D immunoglobulin is typically administered at 28 weeks of gestation and within 72 hours after potentially sensitizing events such as antepartum hemorrhage, miscarriage, or childbirth.
allo-immunisation - testing for other ab?
- Women with a history of blood transfusions, previous pregnancies, or significant red cell alloantibodies are tested for other clinically significant antibodies.
- This helps identify additional risks and guide appropriate management during pregnancy.
acute complications of sickle cell?
- infections
- anaemia
- vaso-occlusive phenomena
- acute painful episodes
- acute chest syndrome
SC: infections?
- Patients are at increased risk of bacterial infections, particularly encapsulated bacteria such as Pneumococcal, Meningococcal and Haemophilus.
- This is due to development of hypo-/asplenism.
CF of infections - SC?
- Clinical features associated with infections are usually organ specific and may include fever, headache, cough, dysuria, abdominal pain and/orrash.
Viral infections w SC?
- Patients are also at risk of viral infections such as parvovirus and influenza.
- Features of coryzal symptoms with a blocked/runny nose, myalgia, arthralgia and/or fever may be present.
how is the infection risk w sickle cell managed?
- Prophylactic penicillin - lifelong
anaemia development with sickle cell?
- ppts usually have a chronic, compensated anemia due to hemolysis
- but symptoms can develop due to acute falls in hb
hyperhaemolysis?
- hyperhaemolysis - sudden exacerbation of haemolysis
- May be associated with acute vaso-occlusive crises, due to excess transfusions and development of alloimmunisation or or coexistence of G6PD deficiency.
splenic sequestration?
- splenic sequestration - life-threatening condition, usually in children.
- Acute fall on Hb due to pooling of red blood cells in the spleen.
- Presents with rapidly enlarging spleen, features of anaemia +/- hypovolaemic shock
3 major causes of an acute drop w sickle cell?
- splenic sequestration
- aplastic crisis
- hyperhaemolysis
aplastic crisis?
- aplastic crisis - transient arrest of erythropoiesis, usually induced by infection (e.g. parvovirus B19)
what are the vaso-occlusive phenomena?
- acute painful episode
- acute chest syndrome
acute painful episodes typically affect?
- typically affects the back, chest, abdomen, extremities and dactylitis - inflammation of a digit (i.e. fingers or toes) may be common in children.
- In severe cases, patients require admission to hospital for parental analgesia (e.g. subcutaneous morphine)
- can occur at the same time as acute chest
how are acute painful epiodes managed?
- analgesia within 30 mins of presentation - opiod + paracetamol and NSAIDs
acute chest syndrome is a life-threatening syndrome characterised by:
- Fever
- Chest pain
- Hypoxaemia
- Wheezing
- Cough
- Respiratory distress
Ix for acute chest?
- CXR: evidence of infiltration usually
Mx of acute chest?
- pain relief
- blood transfusion in the hypoxic patient
- Following an episode of acute chest syndrome the patient should be offered disease modifying therapy (eg hydroxycarbamide, blood transfusion).
splenomegaly and malignancy?
- splenomegaly - can be due to haematological malignancies like lymphoma or leukemia
- can be from metastatic cancer
lymphadenopathy and malignancy?
- lymphadenopathy - Enlarged lymph nodes may be indicative of lymphoma, leukemia, or metastatic cancer spreading via the lymphatic system.
anaemia and malignancy?
- anemia - can result from bone marrow infiltration by cancer cells, chronic inflammation, bleeding
what does MM FBC show?
- FBC typically shows normocytic normochromic anemia due to bone marrow infiltration and suppression of erythropoiesis.
- Leukocytosis or leukopenia may be present.
- Thrombocytopenia can occur due to bone marrow involvement or abnormal platelet function.
ALL FBC?
FBC often shows leukocytosis with lymphoblasts. Anemia and thrombocytopenia are common.
When should myeloma be suspected?
- unex bone pain
- fatigue
- symptoms of hypercalcaemia
- weight loss
- symptoms of cord compression
- symptoms of hyperviscosity
- recurrent infections
symptoms of hypercalcaemia?
- bone pain
- abdo pain
- constipation
- confusion
- polyuria
symptoms of cord compression?
- back pain
- new leg weakness
- bladder/bowel dysfunction
symptoms of hyperviscosity?
headache, blurred vision, shortness of breath, mucosal bleeding
Dx of MM - tests?
- monoclonal ab detection
- bone marrow infiltration - aspiration
- myeloma related organ damage
- staging
MM: ab detection?
protein electrophoresis & immunoglobulins, SFLCs +/- urine electrophoresis for Bence-Jones protein
checking for myeloma related organ damage?
FBC, U&Es, bone profile, imaging (whole body MRI or low-dose whole body CT if MRI not suitable). Skeletal survey (x-rays) only used if CT/MRI not possible
staging for confirmed myeloma?
beta-2 microglobulin, albumin
MM - prognosis?
- Beta-2 microglobulin is often used as a prognostic tool in the International Staging System (ISS) for myeloma - used to stage patients for expected prognosis
what is associated w worse prognosis in myeloma?
- high plasma cell counts
- high levels of monoclonal ab i blood/ urine
- complicatons e.g. diffuse multiple bone lesions, marked anaemia, hypercalcaemia and renal impairment
symptoms of a transfusion reaction?
- fever
- chills
- pruitis
- urticaria
- SOB
- haematuria
what causes non haemolytic (febrile) reactions?
- due to white blood cell HLA antibodies
- often the result of sensitisation by previous pregnancies or transfusions
- paracetamol may be given
what causes acute haemolytic reactions?
- ABO incompatible blood e.g. seconday to human error
- leads to massive intracellular haemolysis
- usually result of red blood cell destruction by igM ab
- symptoms begin minutes after transfusion started
signs of acute haemolytic reactions?
- fever, abd pain, hypotension
Mx of acute haemolytic rection?
- stop transfusion
- confirm diagnosis - send blood for direct Coombs test, repeat typing and cross-matching
- supportive care - fluid resus
what can be seen in febrile non-haemolytic tranfusion reaction ?
- fever, chills
- benign occurance
febrile non HTR is not directly related to?
- not directly related to hemolysis
- caused by cytokine release from leukocytes within donor product as a consequence of WBC breakdown
frequency of FNHTRs increases w?
- frequency of this reaction inc w storage length of donated blood
Testing for transfusion reactions?
- lab Ix - repeat blood typing, crossmatching, complete blood count, coagulation studies, renal function tests, liver function tests, measurement of serum lactate and electrolyte levels
- serological testing - can be performed to detect presence of antibodies in serum that could have caused the transfusion reaction
- includes direct antiglobulin tests - DAT
acute management of DKA - insulin?
In the acute management of DKA, insulin should be fixed rate whilst continuing regular injected long-acting insulin but stopping short actin injected insulin
hyperthyroidism/ hypo and periods?
Hyperthyroidism is associated with oligomennorhoea, or amennorhoea, whereas hypothyroidism is associated with menorrhagia
types of leukemia?
- AML
- Acute lymphoblastic leukemia
- chronic myeloid leukemia
- chronic myeloid leukemia
- chronic lymphocytic leukemia
most cases of leukemia occur in which age group
- most cases occur in ppts over 60-70
which type of leukemia occurs in children under 5
- The exception isacute lymphoblastic leukaemia, which most commonly affects childrenunder five years.
what is the most common leukemia in children?
- acute lymphoblastic leukemia
- assoc w down syndrome
Chronic lymphoblastic leukemia is assoc w ?
- associated w warm haemolytic anaemia and smudge cells
chronic myeloid leukemia is associated w ?
- CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome
AML is associated w?
- AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods
pathophys of leukemia?
- genetic mutation in one of the precursor cells in the bone marrow -> excess production of a single type of abn white blood cell
- The excessive production of a single type of cell can suppress the other cell lines, causing the underproduction of different cell types.
- This can result inpancytopenia, which is a combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia).
presentation of leukemia?
- Fatigue
- Fever
- Pallor due to anaemia
- Petechiae or bruising due to thrombocytopenia
- Abnormal bleeding
- Lymphadenopathy
- Hepatosplenomegaly
- Failure to thrive (children)
initial Ix for leukemia?
- FBC within 48 hrs - initial Ix
- later, blood film used to look for abn cells and inclusions
role of LDH in leukemia?
- lactate dehydrogenase - very non-specific marker of tissue damage. It is often raised in leukaemia but also in other cancers and many non-cancerous conditions, including after heavy exercise. It is not helpful as a screening test but may be used for specialist assessment and monitoring.
what is needed for definitive diagnoses in leukemia?
bone marrow biopsy
LB biopsy?
used to assess abn LNs
other tests for leukemia?
- Genetic tests(looking at chromosomes and DNA changes) andimmunophenotyping(looking for specific proteins on the surface of the cells) may be performed to help guide treatment and prognosis.
bone marrow biopsy is usually taken from the?
- usually from the iliac crest
- aspiration or trephine
what occurs in ALL?
- affects lymphocyte precursor cells cauSing acute proliferation of usually B lymphocytes
- Excessive accumulation of these cells replaces the other cell types in the bone marrow, leading topancytopenia.
ALL can be associated w?
- It can be associated with thePhiladelphia chromosome(but this is more associated with chronic myeloid leukaemia).
what occurs in chronic lymphoblastic leukemia?
- slow proliferation of a single type of well differentiated lymphocyte usually B lymphocytes
- usually affects adults over 60
how does CLL present?
- often asymptomatic but can present with infections, anaemia, bleeding and weight loss.
- It may causewarm autoimmune haemolytic anaemia.
CLL: richter’s transformation?
- Richter’s transformationrefers to the rare transformation ofCLLintohigh-gradeB-cell lymphoma.
CLL blood cell seen on film ?
- Smearorsmudge cellsarerupturedwhite blood cellsthat occur while preparing the blood film when the cells are aged or fragile.
- They are particularly associated withchronic lymphocytic leukaemia.
CML - phases?
- chronic phase
- accelerated phase
- blast phase
chronic phase of CML?
- often asymptomatic, often diagnosed after incidental finding of raised white cell count
- phase can last several years b4 progressing
Accelerated phase of CML?
- accelerated phase - abn blast cells take up 10-20% of the bone marrow and blood cells
- In the accelerated phase, patients are more symptomatic and developanaemia,thrombocytopeniaandimmunodeficiency.
Blast phase of CML?
- follows accelerated phase
- involves over 20% of blast cells in the blood
- The blast phase has severe symptoms andpancytopeniaand is often fatal.
Summary of CML phases?
- chronic -> accelerated -> blast
- chronic: asymptomatic
- accelerated: anaemia and thrombocytopenia
- blast: pancytopenia
CML genetic mutation?
- assoc w philadelphia chromosome
- translocation causes abn gene sequence called BCR-ABL1
when does AML tend to present?
- Normally presents from middle age onwards
AML can be the result of?
- can be the result of a transformationfrom a myeloproliferative disorder, such as polycythaemia ruby vera or myelofibrosis.
blood film results in AML?
- A blood film andbone marrow biopsy will show a high proportion of blast cells.
- Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.
Auer rods characteristic in?
- Auer rodsin the cytoplasm of blast cells are a characteristic finding in AML.
general management of leukemia?
- MDT
- chemotherapy - targeted therapies
Examples of targeted therapies include (mainly used in CLL):
- Tyrosine kinase inhibitors(e.g.,ibrutinib)
- Monoclonal antibodies(e.g.,rituximab, which targets B-cells)
tumour lysis syndrome =
- results from chemicals released when cells are destroyed by chemo resulting in:
- High uric acid
- High potassium (hyperkalaemia)
- High phosphate
- Low calcium (as a result of high phosphate)
electrolyte abn in tumour lysis syndrome?
- hyperkalaemia
- hypocalcemia
- high phosphate
tumour lysis syndrome can lead to?
- uric acid can form crystals in the intersitial space and tubules of the kidneys causing AKI
why can tumour lysis syndrome cause cardiac arrhythmias?
hyperkalaemia
when should TLS be suspected?
should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.
What occurs during lymphoma?
- cancer affecting lymphocytes in the lymphatic system
- cancerous cells proliferate inside the lymph nodes causing them to enlarge - lymphadenopathy
most common type of lymphoma?
- non- hodgkins lymphoma
- It has abimodal age distributionwith peaks around 20-25 and 80 years.
RF for hodgkins lymphoma?
- HIV
- Epstein-Barr virus
- Autoimmune conditions, such as rheumatoid arthritis and sarcoidosis
- Family history
what are the types of non hodgkin lymphoma?
- diffuse large B lymphoma
- Burtkitt lymphoma
- MALT lymphoma
Diffuse large B lymphoma?
typically presents as a rapidly growing painless mass in older patients
Burkitt lymphoma?
particularly associated with Epstein-Barr virus and HIV
MALT lymphoma?
affects themucosa-associated lymphoid tissue, usually around thestomach
what are the RF for non hodgkins lymphoma?
- HIV
- Epstein-Barr virus
- Helicobacter pylori(H.pylori)infection is associated with MALT lymphoma
- Hepatitis B or C infection
- Exposure to pesticides
- Exposure to trichloroethylene(a chemical with a variety of industrial uses)
- Family history
H pylori infection is assoc w
MALT lymphoma
What is key in lymphoma presentation?
- key: lymphadenopathy
- can be in the neck, axilla or inguinal region
- characteristically non-tender and feel firm or rubbery
Patients with Hodgkin’s lymphoma may experience lymph node pain after
Drinking alcohol
B symptomsrefer to systemic symptoms of lymphoma:
- Fever
- Weight loss
- Night sweats
additional non spec symptoms of lymphoma?
- Fatigue
- Itching
- Cough
- Shortness of breath
- Abdominal pain
- Recurrent infections
Ix of lymphoma?
- LN biopsy,
- CT,MRI, andPETscans may be used to help diagnose and stage the disease.
cells which are the characteristic finding from a biopsy of hodgkins lymphoma?
- Reed-Sternberg cellsare the characteristic finding from a biopsy ofHodgkin’s lymphoma. They are large cancerousB lymphocyteswith two nuclei and prominent nucleoli,
Lugano classification of lymphoma?
- used for both types of lymphoma
- Stage 1: Confined to one node or group of nodes
- Stage 2: In more than one group of nodes but on the same side of the diaphragm (either above or below)
- 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
Mx of hodgkins lymphoma?
- chemo
- radio
- curative aim
Mx of non hodgkins lymphoma?
- chemo
- monoclonal ab - e.g. rituximab
- radio
- stem cell transplant
what does myeloma affect?
- Affects the plasma cells in the bone marrow
- Plasma cells are B lymphocytes that produce antibodies
- M protein production
what is multiple myeloma?
- multiple myeloma - when myeloma affects multiple bone marrow areas in the body
monoclonal gammopathy of undetermined significance - MGUS?
- involves production of specific paraprotein w/o other features of myeloma or cancer
- often an incidental finding
- small risk of progression to myeloma
smouldering myeloma?
- involves abn plasma cells and paraproteins but no organ damage or symptoms
- greatest risk of progression to myeloma
pathophys of myeloma?
- Myelomais cancer of a single type of plasma cell, with agenetic mutationthat causes them to rapidly and uncontrollably multiply.
- They produce a specificparaprotein(orM protein), which is an abnormal antibody or part of an antibody (often thelight chain).
findings in myeloma?
- There is an abnormally high level of this paraprotein (paraproteinaemia).
- TheBence Jones proteinrefers tofree light chainsin the urine.
TheCRABmnemonic can be used to remember the four key features of myeloma:
- C–Calcium (elevated)
- R–Renal failure
- A–Anaemia
- B–Bone lesions and bone pain
What is the most common comp of myeloma?
anaemia
why does anaemia occur w myeloma?
- bone marrow infiltration -> suppression of other blood lines -> anaemia, leukopenia, thrombocytopenia
- Anaemia in myeloma isnormocytic andnormochromic
myeloma bone disease?
- increased osteoclast activity and suppressed osteoblast
- -> bone reabs
- -> cytokines released
- Common sites of myeloma bone disease are the skull, spine, long bones and ribs.
what can myeloma bone disease lead to?
- The abnormal bone metabolism is patchy, meaning that the bone becomes very thin in some areas while others remain relatively normal.
- These patches of thin bone are described asosteolyticlesions.
- These weak points in the bone lead topathological fractures.
- inc osteoclast -> hypercalcaemia
enal disease from myeloma - causes?
- Paraproteinsdeposited in the kidneys
- Hypercalcaemiaaffecting kidney function
- Dehydration
- Glomerulonephritis(inflammation around the glomerulus and nephron)
- Medicationsused to treat the condition
hyperviscosity syndrome?
- plasma viscosity increased when more proteins are in blood such as the paraproteins found in myeloma
- medical emergency
what can hypervis syndrome cause?
- Bleeding (e.g., nosebleeds and bleeding gums)
- Visual symptoms and eye changes (e.g., retinal haemorrhages)
- Neurological complications (e.g., stroke)
- Heart failure
RF for myeloma?
- Older age
- Male
- Black ethnic origin
- Family history
- Obesity
features of myeloma?
- Persistent bone pain (e.g., spinal pain)
- Pathological fractures
- Unexplained fatigue
- Unexplained weight loss
- Fever of unknown origin
- Hypercalcaemia
- Anaemia
- Renal impairment
Ix results for myeloma?
- FBC - anaemia or leukopenia
- calcium is raised in myeloma
- ESR raised
- Plasma viscosity
other tests for myeloma?
- U&E( for renal impairment)
- Serum protein electrophoresis(to detect paraproteinaemia)
- Serum- free light-chain assay( to detect abnormally abundantlight chains)
- Urine protein electrophoresis(to detect theBence-Jones protein)
what is required to confirm myeloma diagnosis?
bone marrow biopsy
Imaging used for bone lesions in myeloma?
1) whole body mRI
2) whole body low dose CT
3) X ray
XR findingsin myeloma?
- Well-defined lytic lesions (described as looking “punched-out”)
- Diffuse osteopenia
- Abnormal fractures
raindrop skull?
Raindrop skull(sometimes calledpepper pot skull) refers to multiple lytic lesions seen in the skull on an x-ray.
Mx of myeloma?
- chemo
- stem cell transplant
Mx of myeloma - bone lesions?
- Bisphosphonates to suppress osteoclast activity
- Radiotherapy for bone lesions can improve bone pain
- Orthopaedic surgeryto stabilise bones (e.g., by inserting a prophylactic intramedullaryrod) or treat fractures
- Cement augmentation(injecting cement intovertebral fracturesorlesions) to improve spine stability and pain
complications of myeloma?
- infections
- bone pain
- fractures
- anemia
- hypercalcaemia
- peripheral neuropathy
- spinal cord compression
- hyperviscosity syndrome
- venous TE
what is indication for pulm oedema?
Pulmonary oedema is an indication for haemodialysis in a patient with acute kidney injury
systemic infections from chemo?
- Febrile Neutropaenia (Neutrophil < 1.0 x 109/L and Temperature > 38oC)
- Septic Shock (low Blood Pressure)
management of neutropaenic sepsis
- IV fluids
- broad spectrum ab
management of emesis from chemo?
- serotonin antagonist and dexamethasone
- domperidone
management of alopecia from chemo?
- always reversible
- caused by drugs like athracycline and taxanes
- can be ameliorated by scalp cooling
which chemo agents can caue peripheral neuropathy?
- Cisplatin, Oxaliplatin
- Vinca alkaloids
- Taxanes
sites affected by peripheral neuropathies?
- Hands and feet
- Autonomic system
- Tends to be cumulative i.e. get worse with increasing cumulative dose
- Tends to be irreversible
Which agents
chemo induced sterility?
- tends to occur when alkylating agents are used
- spont recovery can occur in younger ppts
- sperm storage should be offered for males
which cytotoxic drugs are most likely to cause cardiac problems?
- Anthracylines are the cytotoxic drugs that most commonly cause cardiac problems which are usually manifested by congestive heart failure but this is rare if the cumulative dose is kept below a certain cumulative dose level
- Many drugs e.g. Taxanes and Anthracylines can cause arrhythmias
anticipatory drugs at the end of life ?
- pre-emptive prescribing
- prescription of drugs that may be needed for symptom management at the end of life
- symptoms may not be present yet
- all given subcutaneously
- syringe driver if they can’t swallow
common indications for syringe drivers?
- persistent nausea and vomiting
- severe dysphagia
Drugs used for RT secretions?
- anti-muscarinics e.g. hydrobromide or glycopyrronium
first line for EOL restlessness/ agitation?
- midazolam first line
- lorazapam can be used to relieve anx/ fear
EOL: delirium?
- Acute confused state characterised by cognitive impairment and mental clouding, Fluctuant
- May include hallucinations, aggression, plucking and increased or decreased psychomotor activity
- haloperidol
first line for EOL vomiting?
- haloperidol first line
- or metoclopramide
SOB management - EOL?
- opiods
- benzos: 2nd line
Tool used to decide when a person needs a palliative care approach?
SPICT tool to decide when a person needs a palliatiev care approach
What is advanced care planning?
- process of discussion between and indiv and their care providers
- facilitates and enables individuals to think abt the care that they would like to receive
- allows them to choose where they want to die
what is the benefit of ACP?
- ppt has to be ready
- patient centered
- prevents over-treatment when the patient lacks capacity
EOL care plan ensures?
EoL care plan: ensures best quality of care during the patients last days
Advanced care planning allows for?
- advanced care planning allows for personalised care plans, patient orientated care
how does cytotoxic chemotherapy work?
- works by interfering with the cell division process, targeting rapidly dividing cells
- Chemotherapeutic agents disrupt various stages of the cell cycle, leading to DNA damage, inhibition of DNA synthesis, or interference with microtubule function, ultimately resulting in cell death.
how does targeted therapy work?
- Targeted therapy involves drugs that selectively target specific molecular alterations or pathways involved in cancer growth and survival, sparing normal cells.
- Targeted therapies exploit genetic and molecular differences between cancer cells and normal cells to inhibit key signaling pathways or molecular targets driving tumor growth.
how does hormone therapy work?
- Hormone therapy aims to block or interfere with hormone signaling pathways that promote the growth and survival of hormone-sensitive cancers, such as breast or prostate cancer.
- Hormone therapy targets hormone receptors (e.g., estrogen receptor, androgen receptor) or inhibits hormone production to suppress tumor growth and induce cancer cell death.
how does immunotherapy work?
- Immunotherapy enhances the body’s immune response to recognize and destroy cancer cells by targeting immune checkpoints, stimulating immune cell activation, or enhancing tumor-specific immune responses.
- Immunotherapy drugs, such as immune checkpoint inhibitors, monoclonal antibodies, or adoptive cell therapies, harness the immune system’s ability to recognize and eliminate cancer cells.
Rationale for chemo?
- targets rapidly dividing cells by disrupting various stages of the cell cycle leading to DNA damage
- aims to induce apoptosis in actively proliferating cancer cells while sparing normal cells
- Chemotherapy drugs primarily target rapidly dividing cells, including cancer cells, but can also affect normal cells with high turnover rates, such as bone marrow cells and gastrointestinal epithelial cells.
Rationale for targeted therapy?
- biological rationale: specifically inhibits molecular targets or signaling pathways that are dysregulated in cancer cells, while minimizing effects on normal cells.
- Targeted therapy drugs exploit genetic and molecular differences between cancer cells and normal cells to block key signaling pathways involved in tumor growth, survival, and angiogenesis.
- can target specific molecular alterations such an oncogenes, signal pathways, tumor suppressor genes
Rationale for hormone therapy?
- targets hormone receptors or inhibits hormone production to suppress the growth and survival of hormone-sensitive cancers
- Hormone therapy exploits the dependence of certain cancers (e.g., breast cancer, prostate cancer) on hormones, such as estrogen or androgen, for growth and proliferation.
- targets hormone receptors like ER, PR, androgen receptors to block hormone signalling and inhibit tumor growth
Rationale for immunotherapy?
- Immunotherapy harnesses the body’s immune system to recognize and eliminate cancer cells by enhancing immune responses against tumor antigens.
- Immunotherapy drugs modulate immune checkpoints, stimulate immune cell activation, or enhance tumor-specific immune responses to overcome immune evasion mechanisms employed by cancer cells.
- Targets: Immunotherapy targets immune checkpoints, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), to unleash antitumor immune responses.
Why is bone marrow susceptible to chemo?
- primary site of hematopoiesis - rapid turnover rate
- cytotoxic therapies target rapidly dividing cells by disrupting DNA synthesis making the bone marrow susceptible to toxic effects
- bone marrow suppression can lead to anemia, leukopenia, thrombocytopenia
why is GI epithelium susceptible to chemo?
- high cell turnover rate
- Chemotherapy drugs can affect rapidly dividing cells in the gastrointestinal epithelium, leading to mucositis, diarrhea, nausea, and vomiting.
- -> ulceration, mucosal inflammation, impaired nutrient abs
why is hair susceptible to chemo?
- rapid division
- can lead to alopecia by inducing apoptosis
physical side effects of chemo?
- bone marrow suppression: anemia, leukopenia, thrombocytopenia
- GI toxicity: nausea, vomiting, diarrhea, constipation, mucositis, loss of appetite
- alopecia
- peripheral neuropathy - numbness, tingling, or pain in the hands and feet.
cardio and pulm side effects of chemo?
- cardiotoxicity - cardiotoxic effects, leading to heart failure or arrhythmias.
- pulm toxicity - lung toxicity -> SOB/ cough
psych side effects of chemo?
- anxiety/ depression - uncertainty abt future, stress of cancer diagnosis
- body image concerns - hair loss, weight changes
- cognitive impairment - chemo brain
- fear of reccurence
social side effects of chemo?
- social isolation - treatment may limit a patient’s ability to participate in social activities due to fatigue, nausea, or other physical symptoms.
- financial - time off work
- impact on relationships - change in relationship dynamics
Myelosuppression - anaemia - signs?
- Signs: Fatigue, weakness, pallor (pale skin), shortness of breath, dizziness, headache.
myelosuppression - anaemia - symptoms?
- Symptoms: Feeling tired or lethargic, difficulty concentrating, increased heart rate (tachycardia).
Myelosuppression - leukopenia - signs?
- Signs: Increased susceptibility to infections, frequent fevers or chills, persistent sore throat, mouth sores, skin infections or abscesses.
myelosuppression - leukopenia - symptoms?
- Symptoms: Fever, chills, body aches, malaise (general feeling of illness), swollen lymph nodes
Neutropenia from myelosuppression?
- neutropenic fever - medical emergency
- Symptoms: Fever (temperature > 38.3°C or 101°F), shaking chills, rapid heartbeat, low blood pressure, rapid breathing, confusion or altered mental status.
signs of thrombocytopenia (myelosuppression))
- Signs: Easy bruising, petechiae (small red or purple spots on the skin), prolonged bleeding from minor cuts or injuries, nosebleeds, bleeding gums.
symptoms of thrombocytopenia from myelosuppression?
- Symptoms: Excessive bleeding from wounds, gums, or nose, blood in urine or stool, heavy menstrual bleeding, prolonged or heavy bleeding after minor trauma.
managing alopecia?
- scalp cooling
ppts taking which chemo agent need to be asssed for paralytic ileus?
- patients receiving vinca alkaloids need to be assessed for paralytic ileus which would present with constipation and absence of bowels sounds, ultra sound may be indicated.
- This is a medical emergency due to the risk of perforation.
what are the vibca alkaloids?
- vinca alkaloids - (vincristine, vinblastine and vinorelbine)
Mx of constipation from chemo?
- advice on:
- maintaining adequate fluid intake
- maintaining healthy high fibre diet
- gentle exercise
- movicol
- docusate sodium
diarrhoea is linked to which chemo agentS?
- linked to 5FU and methotrexate
treatment of diarrhoea from chemo?
- loperamide
- coedine phosphate
management of oral thrush from chemo?
- Nystatin suspension
- fluconazole
what are highly emetic chemo agents?
- cisplatin and cyclophosphamide
Mx of chemo related emesis?
- low risk: dexamethasone
- moderate risk: 5-HT3 antagonist
- high risk: dexamethsaone, 5-HT3 antagonost, NK1 antagonist e.g. aprepitant
signs of a bleeding tendency?
- easy bruising
- bleeding gums
- heavy bleeding from small cuts or dental work
- unexplained nosebleeds (Epistaxis)
- heavy menstrual bleeding
- bleeding into joints
- excessive bleeding following surgery
- petechiae - small red or purple spots on the skin or mucous membranes resulting from bleeding under the skin
- purpura - larger areas of discoloration similar to brusing but covering a larger SA
- haematuria
- melena
- haematemesis
- haemoptysis
History for a bleeding tendency?
- personal history of bleeding episodes
- family history
- history of bleeding after surgical or dental procedures
- medication history - warfarin, heparin, aspirin, clopidogrel, NSAIDs
- menstrual history
- lifestyle factors - participation in contact sports, occupation-related risks (e.g., heavy manual labor), or habits such as alcohol consumption or recreational drug use that can affect coagulation.
polycythemia vera?
- JAK2 mutation
- caused by clonal proliferation of a marrow stem cell leading to increase in red cell volume
- often overproduction of neutrophils and platelets
PV - hyperviscosity?
- overproduction of BC -> hypervisc
- inc risk of thrombotic events such as DVT, PE, arterial thrombosis
- congestion and engorgement of organs -> hepatomegalt and splenomegaly
Features of polycythemia?
- hyperviscosity
- pruitus
- splenomegaly
- haemorrhage
- plethoric appearance
- HTN
Mx of PV?
- Venesection - first line
- hydroxyurea
- P32 therapy
typical PV features?
hyperviscosity, pruitus and splenomegaly
Myelofibrosis?
- rare haem disorder where bone marrow is replaced by collagen and becomes fibroised
-> splenomegaly, fatigue, extramedullary haematoposis
what can transform into AML?
myelofibrosis
Myelofibrosis CFs?
- severe fatigue
- hepatosplenomegaly - so profound it can extend past mildine
- B symptoms
- signs of anaemia
- thromboembolic events
- unexp bleeding
Immune thrombocytopenia?
- ITP
- most common cause
- caused by low platelet count due to destruction of platelets by autoab
How can ITP present?
can be acute or chronic and may present with petechiae, ecchymoses, or mucosal bleeding.
drug induced thrombocytopenia?
- heparin
- quinine
- sulfonamides
Haemolytic uremic synrome?
- characterized by microangiopathic hemolytic anaemia, thrombocytopenia, and acute renal failure.
- It is most commonly caused by infection with Shiga toxin-producing Escherichia coli.
Disseminated intravasc coagulation?
- characterized by widespread activation of the coagulation system, leading to the formation of microthrombi and consumption of platelets and clotting factors.
- caused by sepsis, trauma, malignancy
Features of myelofibrosis?
- e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
- massive splenomegaly
- hypermetabolic symptoms: weight loss, night sweats etc
Lab findings in myelofibrosis?
- anaemia
- high WBC and platelets early in disease
- tear drop poikilocytes on blood film
Myelodysplastic syndrome?
- characterised by ineffective haematopoiesis, peripheral blood cytopenias and risk of progress to AML
myelodysplasia disorder Sx?
- fatigue
- weakness
- pallor
- reccurent infections due to neutropenia
- easy bruising due to thrombocytopenia
Diagnosis of myelodysplastic disorder?
Bone marrow biopsy typically shows dysplastic changes in hematopoietic cells and a varying degree of blasts
