Blood Disorders Flashcards
A patient’s blood results show high Eosinophils. What could that indicate?
Allergic reaction or Asthma
(=Eosinophils participate in the inflammatory response of these 2 scenarios)
A patient’s blood results show high Neutrophils. What could that indicate?
1.Infections usually due to bacterial / Fungi / Parasitic causes.
2.Corticosteroids can also cause an increase
A patient’s blood results show high Basophils. What could that indicate?
1.Peristant Infections such as Influenza or TB
2.Allergies
3.Could be more serious: Hyperthyroidism or Cancer
If a patient is smoking, what happens to the RBC levels and why?
INCREASE:
Carbon monoxide from the cigarettes has a higher affinity for haemoglobin than O2 therefore there is less bound O2. Less O2 levels triggers the production of Erythropoietin from the kidneys which increases RBC production.
If there are high Basophils, what effects would you expect in terms of blood clotting?
Decrease in clot formation as Basophils release Heparin which prevents clotting.
Why can’t a pregnant woman towards the end of
her pregnancy not be able to take Aspirin?
Aspirin inhibits prostaglandin synthesis which therefore inhibits thromboxane synthesis. Thromboxane is required for platelet activation and vascular spasm (closing of blood vessels) and so by inhibiting this, during labour, less clotting would mean EXCESSIVE bleeding putting both Mum and Baby at risk.
A patient has a suspect heart attack. What medication would usually be given on route to the hospital in the ambulance and why?
Aspirin
=to reduce clotting that has most likely caused a heart block
What is gold star treatment of clots in hospitals?
Streptokinase
What is the pathophysiology of Haemolytic Disease of the Newborn?
When a RH- mother has a baby that is RH+. The mother produces antibodies to destroy the baby’s RBCs. This is mainly common in second, third etc pregnancies since the first pregnancy would not be enough time for antibody production. Baby’s life is therefore at risk or if born will need to treatment to reverse these issues.
A baby is born with Hemolytic Disease. What are the treatments?
1.Phototherapy
=to treat the Jaundice (Bilirubin from destruction of their RBCs)
2.Exchange transfusion (RH- blood)
3. Erythropoietin
=(treats the anaemia)
What are the causes of Secondary Erythrocytosis?
DECREASED O2 LEVELS by:
-High Altitudes
-Chronic Obstructive Pulmonary Disease (COPD)
-Congestive Heart Failure
What is Erythocytosis?
An overabundance of RBCs increasing blood viscosity which causes reduced blood flow and severely plugged capillaries.
What is Primary Erythrocytosis?
Also known as Polycythemia Vera.
-Increased RBCs and decreased blood flow
How is Erythrocytosis treated?
Phlebotomy - removal of RBCs
An athlete has been blood doping. What is a serious complication of this?
Erythocytosis
Name some symptoms of Erythrocytosis?
Headaches.
blurred vision.
red skin, particularly in the face, hands and feet – this may be more difficult to see on black or brown skin.
tiredness.
high blood pressure.
dizziness.
discomfort in the tummy.
confusion.
What is the Haematocrit measurement?
The percentage of blood volume that is RBCs.
What are the causes of Aplastic Anaemia?
Remember mneumonic
CARB mneumonic
-Chloramphenicol (Broad-spectrum Antibiotic)
-Autoimmune destruction of red marrow stem cells (therefore less production of RBCs)
-Radiation / Chemotherapy
-Benzene exposure e.g Car Exhaust / Cleaning products, Paint, Glue
What is the most common type of anaemia for a smoker?
Iron-deficiency anaemia (due to the carbon monoxide binding the haemoglobin instead of O2)
What are the symptoms of aplastic anaemia?
Usual anaemia symptoms - pale and tired
+Frequent infections
+Dyspnoea during exertion
Aplastic anaemia is less RBCs due to less production which means less O2 transport and as RBCs acts as biochemical barriers to infection, less RBCs means more infection.
A high MCV of 80-100 would indicate which pathologies?
Haemolytic anaemia and aplastic anaemia
What blood test results would be expected from a patient with aplastic anaemia?
HIGH MCV and Low Reticulocytes (immature RBCs)
What does MCV measure?
Size of your RBCs
What blood results are expected for iron deficiency anaemia?
LOW MCV and MCHC
A pregnant woman has suspected Folate deficiency anaemia. What would you expect the MCV to be like and what would you do next?
-MCV could be either high or normal.
-Cobalamin test is required even if MCV is normal to test for B12 and therefore the potential neurological impacts (e.g Spina Bifida)
What is Colabamin testing?
Testing for B12
What is produced to facilitate B12 intestinal absorption and where is it made?
Intrinsic Factor from the stomach
What is the pathophysiology of Pernicious anaemia?
B12 deficiency which is usually caused by an autoimmune response destroying the cells of the stomach that produce intrinsic factor.
What are the common causes of an increased Prothrombim time?
Remember pneumonic
Don’t Lengthen Afghanistan’s War
1.Deficiency (of Vit K)
2.Liver disease
3. ALL Antibiotics
4. Warafin
What can decrease Prothrombin time?
Vitamin K, Oral contraceptive pill
What would you expect of the MCV for a patient with iron deficiency anaemia?
Low - i.e Microcytic
Name common types of microcytic anaemia.
1.Iron deficiency anaemia
2.Thalassaemia
3.Sideroblastic anaemia (but can also be normocytic)
Name common causes of macrocytic anaemia.
Remember mneumonic
Many Parties Allow Copious Alcohol
1.Methotrexate
2.Pernicious Anaemia
3.Anti-convulsant
4.Cancer (Myelodysplastic)
3.Alcohol
What group of people are at risk of iron deficiency anaemia?
Pre-menopausal anaemia (due to increased menstrual bleeding)
What is the most common cause of anaemia in men and post-menopausal women?
GI bleeding
Name 2 clinical signs of iron deficiency anaemia?
Koilonychia (spoon shaped nails)
-Angular chelitis (thickening of skin around lips at the side)
A patient with suspected anaemia has chest pains and shortness of breath. Could this still be anaemia?
Yes, but these symptoms only develop in late and progressed anaemia
What is another name for Plummer-Vinson Syndrome?
Paterson-Kelly-Brown Sydrome
What are the classical triad of symptoms for a patient with Paterson-Kelly Brown Syndrome?
1.Iron Deficiency Anaemia
2.Oesophageal Webs (thin membranes within the upper oesophagus causing difficulty swallowing)
3.Dysphagia
What is the treatment for Plummer-Vinson Syndrome?
-Iron replacement
-Endoscopic dilatation
+Monitoring for Oesophageal cancers
What is diagnostic of iron deficiency anaemia?
Low Serum Ferritin
When can serum ferritin be falsely elevated?
During an inflammatory illness - this would raised
What is the stepwise management for iron deficiency anaemia?
1.Oral Iron Replacement:
-Ferrous Sulphate / Fumarate
A patient is put on iron replacement. What should they be warned of?
-Black stools
-Constipation
-Nausea
What is the treatment for Thalassaemia?
Blood transfusions
+Iron Chelation (to reduce iron overload from the transfusion)
=Desferrioxamine (subcutaneous)
What is used to treat congenital Sideroblastic Anaemia?
Pyridoxine
B6vitamin that will supports proper development of RBCs as it is important for Haem Synthesis. Works within 2 weeks.
What is Sideroblastic Anaemia?
Dysfunctional Erythropoiesis leading to excess iron deposition
What are the causes of acquired Sideroblastic Anaemia?
Remember mneumonic
Sideroblastic Anaemia Angers Life
-Systemic Lupus Erythematosus
-Alcohol
-Antibiotics
-Lead poisoning
What are the 3 causes of B12 insufficiency ?
1.Dietary e.g Vegetarians and Vegans
2.Gastric Pathology (e.g pernicious anaemia)
3.Small bowel pathology (Inflammatory Bowel Disease, Malabsorption disorders e.g Small Intestine Bacterial Overgrowth)
What are the causes of folate deficiency?
Remember mneumonic
Men Deficient in Proper Manners Might Tremble
1.Metabolic demand increased (pregnancy, proliferative diseases, malignancy)
2.Diet (alcohol and malnutrition)
3.Phenytoin (drug for seizures)
4.Methotrexate
5.Malabsorption disorders (e.g Irritable Bowel Disease, Small Intestinal Bacterial Overgrowth)
6.Trimethoprim (drug for UTIs)
Name 3 common iron chelators and what do they do?
=To prevent iron overload in patients getting regular blood transfusions
1.Deferasirox (oral)
2.Deferiprone (oral)
3.Desferrioxamine (subcutanous)
All start with Des/Def -
The Ox is Prone to Amines
What are the symptoms of a folate deficiency?
Usually asymptomatic but can present with
GLOSSITIS
=Inflammation of the tongue
What is the pathophysiology of Pernicious Anaemia?
Atrophic gastritis and destruction of parietal cells (that produce intrinsic factor)
NOTE: Intrinsic factor is required for B12 reabsorption so this causes a deficiency of B12
What is the average onset for Pernicious Anaemia?
60 and above
What autoimmune conditions can secondarily cause Pernicious Anaemia?
-Addison’s disease
-Vitiligo
-Hashimoto’s Thyroiditis
-Grave’s Disease
Think ENDOCRINE!
A patient has Pernicious Anaemia. What investigation is required to monitor for what potential serious complication?
Upper GI endoscopy for Gastric Tumour monitoring
What is the management for B12 deficiency?
6 doses over 2 weeks of IM B12 injections
What are the 5 sickle cells crises / presentation (if not diagnosed at birth)?
1.Vaso-Occlusive Crisis
=skeletal pain due to necosis of bone marrow - fingers is common for children (Dactylitis) and torso bone pain for adults
2.Blood vessel crisis e.g Bowel ischaemia, renal papillary necrosis, retinal haemorrhage / detachment, cerebral infarction
3.Sequestration crisis
=Splenomegaly, Pallor
4.Acute chest syndrome
=Vaso-occlusion of the lungs (seen on CXR) presenting chest pain, fever, dyspnoea
3.Aplastic Crisis
=Severe anaemia causing a similar clinical picture to heart failure
What is given to patients with sickle cell anaemia?
Hydroxyurea (increases concentration of Hb)
-bone marrow replacement in children
What is the treatment for Aplastic Anaemia for young patients (under 50s) and Elderly (over 50)?
Under 50s:
-Allogenic Stem Cell treatment
–>curative
Over:
-Immunotherapy (Cyclosporin and Antithymocyte globulin)
–>improves survival
For remembering Immunotherapies:
-Cylone Spores
-Aunty Thyme -ocyte
What is the main major complication of Hereditary Spherocytosis?
Gallstones
=The red cell lysis causes an accumulation of unconjugated bilirubin which can therefore cause Gallstones
What is the line of inheritance for Hereditary Spherocytosis?
Autosomal dominant
What is Hereditary Spherocytosis?
Inherited haemolytic anaemia where defects in protein synthesis increase RBC fragility and therefore haemolysis develops.
How is Hereditary Spherocytosis diagnosed?
Peripheral blood film - presence of Spherocytes.
What is the presentation of a patient with Hereditary Spherocytosis (incl onset)?
Present at birth:
-Jaundiced
-Splenomegaly (most not all)
-Megaloblastic crisis (folate deficiency)
-Aplastic crisis due to B19 Parvovirus
Megaloblastic crisis
What haematological crisis can a B19 Parovirus cause (usually in children)?
Aplastic Anaemia Crisis
What is the treatment for Hereditary Spherocytosis?
1.Folate replacement and splenectomy AFTER THE AGE OF 6
A 3year old is being considered for a Splenectomy. What should be considered and why?
Operation not until 6years old due to risk of SEPSIS.
What is given post-splenectomy and for how long?
For at least 2 yrs after operation.
Vaccines:
-Pneumococcal vaccine
-Meningococcal ACWY conjugate vaccine -Meningococcal B vaccine
Antibiotics:
Amoxycillin or Clarithromycin
-Patients should always have access to these to take immediately after signs of an infection
What is the inheritance for Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
X linked
(more common in men)
What is the pathology of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Deficiency of G6PD means there is an intolerance of oxidative stress and therefore increasing haemolysis.
–>Haemolysis is triggered by drugs, acute infection and exposure to certain substances.
In Glucose-6-phosphate dehydrogenase (G6PD) deficiency, what are the triggers for haemolysis?
Drugs:
-Antimalarials (Chloroquine phosphate).
-Aspirin
-Antibiotics
-Vitamin K
Acute Infection
Exposure:
-Broad / Fava Beans
-Moth balls
What is the presentation of a patient with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Jaundice and anaemia
A patient with Glucose-6-phosphate dehydrogenase (G6PD) deficiency has a blood film come back after a suspected acute attack. What would you expect to see?
Blister (/bite) cells and Heinz bodies
-may also see elevated reticulocyte count
A patient has suspected G6DP. What tests should be done / considered?
-Blood film
(look for Blister cells and Heinz bodies, elevated reticulocyte count)
What is the management of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Acute transfusions in SEVERE cases
-stop triggers and treat underlying cause (acute infection)
What is inheritance of Pyruvate Kinase Deficiency?
Autosomal Recessive
What is the pathology of Pyruvate Kinase Deficiency?
Embden-Meyerhof glycolytic pathway is affected causing reduced ATP synthesis which causes red cells to be RIGID.
A patient has suspected Pyruvate Kinase Deficiency, what investigation should be done and what result would you expect?
Blood film
=Prickle cells
What is the presentation of a patient with Pyruvate Kinase Deficiency?
Variable of splenomegaly and anaemia.
What is the management for Pyruvate Kinase Deficiency?
Possible transfusions and splenectomy if the patients needs regular transfusions
What is the Coombs Test and what does it diagnose?
An antiglobulin test to detect presence of antibodies.
- DAT coombs is for testing for Haemolytic anaemia and Transfusion reactions, while
-IAT is for prenatal rhesus testing and blood cross matching
A patient has intermittent episodes of jaundice and anaemia. What does that indicate?
Haemolysis
A patient has intermittent episodes of jaundice and anaemia as well as splenomegaly. What test would you think would be diagnostic of your suspicions?
DAT Coombs test to diagnose Haemolytic Anaemia (specifically autoimmune anaemia)
A patient with jaundice and anaemia presents with their extremities (hands) with painful and blue areas. What antibody would you expect to find and what type of disease would this be?
IgM
=Chronic Cold Agglutinin Disease (CHAD)
WHICH IS A TYPE OF AUTOIMMUNE HAEMOLYTIC ANAEMIA
What age bracket usually would be seen to have Chronic Cold Agglutinin Disease (CHAD) ?
Elderly
What antibody would you expect to see in a patient with suspected warm autoimmune haemolytic anaemia?
IgG
What is the difference between warm and cold autoimmune haemolytic anaemia?
The temperature refers to when the antibodies are active.
-Cold is due to IgM antibodies present and activated in the cold
-Warm is due to IgG antibodies being present and activated at body temperature
Who is most commonly affected by warm autoimmune haemolytic anaemia?
Middle aged females
What are the causes of warm autoimmune haemolytic anaemia?
Remember mneumonic
Idiotic Pensive Neds Ruminate with Meth Limes
1.Idiopathic (usually)
2.Penicillin
3.Nsaids
3.Rheumatic conditions (e.g Lupus)
5.Methyldopa (used for pre-eclampsia i.e hypertension)
5.Lymphoid malignancy
What are the causes of cold autoimmune haemolytic anaemia?
Remember mneumonic
Ill Patients May Even Live
1.Idiopathic
2.Paroxysmal nocturnal haemoglobinuria
3. Mycoplasma
4. Epstein Baar Virus
5.Lymphoid malignancy
What is the management for warm autoimmune haemolytic anaemia?
-Treat underlying cause AND
1.Corticosteroids BUT TAKES 3WEEKS TO WORK
2.Splenectomy considered if not responding to corticosteroids
What are the causes of non-immune acquired haemolytic anaemia?
-Malaria, Clostridium Perfringens
-Acquired membrane defect : Paroxysmal Nocturnal Haemoglobinuria
-Mechanical Heart Valves
-Microangiopathic Haemolytic anaemia (fibrin deposition in capillaries)
-ITP (Idiopathic Thrombocytopenia Purpura)
-Burns causing injury
What is Paroxysmal Nocturnal Haemoglobinuria?
=Rare Acquired Haemolytic anaemia type that causes:
-Intravascular haemolysis
-Thrombosis (venous and arterial)
-Deficient haematopoiesis
What is the management for Paroxysmal Nocturnal Haemoglobinuria?
Supportive care
-intermittent blood transfusions
-long term anticoagulation
-Eculizumab (stops the antibody responsible)
-
In terms of presentation, what are the differences between a clotting and coagulation disorder?
Site:
-Clotting = bleeding within skin (bruising and purpura) or mucosal membranes (GI, uterine)
-Coagulation=bleeds involves joints (Haemarthroses) or Muscles (Haematoma)
Onset:
-Clotting= occurs spontaneously
-Coagulation = occurs within hours to days
What is Haemarthroses and how does it present?
Bleeding into articular spaces (between bones at the joints). Common in patients after an injury or with Haemophilia.
=swelling and pain at the joint region
What clinical disorder is a platelet count especially screening for?
Thrombocytopenia
What clinical disorder is a bleeding time especially screening for?
-Platelet dysfunction
-Von Willibrand Disease
What is a Activated Partial Thromboplastin Time looking especially for?
-For monitoring Heparin therapy, Warafin therapy, Haemophilia, Disseminated intravascular coagulation, Liver disease
What is the inheritance for Hereditary Haemorrhagic Telangiectasia?
Autosomal Dominant
What are the 2 clinical signs of Hereditary Haemorrhagic Telangiectasia?
-Telangiectasia
= tortuous dilatation of end-capillaries seens in the fingers, toes, lungs, GI tract and nose
-Arteriovenous Malformations
=shunting of blood flow
What is the presentation of a patient with Hereditary Haemorrhagic Telangiectasia?
-Recurrent epistaxis
-GI bleeds
=Iron deficient anaemia
A patient has recurrent epitaxis as well as red spots on the lips. What tests should be done and why?
Potentially Hereditary Haemorrhagic Telangiectasia
=AVM (Arteriovenous malformations) Screening
What is the most common cause of Thrombocytopathy?
DRUGS:
-Antiplatelets: Aspirin, Clopidogrel
-Glycoprotein inhibitors
What diseases can cause Thrombocytopathy?
Renal and liver disease
What are 2 congenital Thrombocytopathy disorders?
1.Glanzmann thrombasthenia
-Bernard-Soulier Syndrome
What is a Thrombocytopathy?
Platelet dysfunction
What is a Thrombocytopenia?
Reduced platelet count
What is Idiopathic Thrombocytopenia Purpura?
Autoimmune condition characterised by low platelet count (in the absence of other causes)
Describe the typical presentation of a patient with Idiopathic Thrombocytopenia Purpura?
-Often triggered by infection
-self limiting in children
-chronic and sudden onset in adults
-bleeding gums and easily bruising etc
What are the investigations for a suspected case of Idiopathic Thrombocytopenia Purpura?
-FBC
-Blood film
-Bone marrow biopsy in those over 60
What results would expect from investigations into a potential Idiopathic Thrombocytopenia Purpura?
-Everything normal apart from LOW PLATELETS
What is the management for Idiopathic Thrombocytopenia Purpura?
Acute attacks:
-Short course of Corticosteroids
Severe cases:
+Adjunct = IV Ig
A patient with Thrombocytopenia is to be started on Heparin. What should be considered and therefore investigated before prescribing?
4T score can indicate the likelihood of Heparin-induced Thrombocytopenia which could develop after 5-10 days after starting on Heparin.
Which Heparin is more likely to cause Heparin-induced Thrombocytopenia?
Unfractionated while Low molecular weight is much safer!
What is the inheritance for Haemophilia A?
X linked Recessive
=almost exclusively affects MALES
What clotting factor is affected in Haemophilia A?
VIII
What is the pathophysiology of Haemophilia A?
VIII mutation means reduced circulating factor which is required for formation of THROMBIN resulting in ABNORMAL COAGULATION (more bleeding)
How does Haemophilia A affect a coagulation screen?
Increased Activated Partial Thromboplastin time (aPTT)
What type of bleeding and complications can a patient with severe Haemophilia A get?
Type of bleeding:
Spontaneous bleeding most commonly into joints (Haemarthroses) and Haematomas
Complications:
=Haematomas of the Psoas and calf muscles can causes FEMORAL NERVE COMPLICATION, COMPARTMENT SYNDROME
=RECURRENT HAEMARTHROSIS can cause CARTILAGE DESTRUCTION AND JOINT DEFORMITIES
What is the management for acute major bleeds due to Haemophilia A ?
IV Plasma derived or Recombinant factor VIII
What is the management for minor bleeds due to Haemophilia A ?
IV or Intranasal Desmopressin (DDAVP)
What is DDAVP and how does it work?
Desmopressin which indirectly increases the release of Von Willebrand Factor and levels of factor VIII
What lifestyle advice should be given to a patient with Haemophilia A ?
-Avoid contact sports
-Avoid NSAIDs
-AVOID IM Injections
What are the key symptoms that suggest a clotting defect?
-Epistaxis (nose bleed)
-Menorrhagia (increased menstrual bleeding)
-Bleeding post surgery
What coagulation results would you expect from a patient with Haemophilia A ?
Increased Bleeding Time and APTT
What is the treatment for mild/moderate cases and severe cases of Von Willebrand disease?
Mild/Moderate
=DDAVP (Desmopressin)
Severe
=Intermediate Purity factor VIII concentrate
What is the inheritance for Von Willebrand disease?
Type 1 and 2 = autosomal dominant
Type 3 = autosomal recessive
In terms of symptoms what are the differences between Type 1, 2 and 3 Von Willebrand disease?
Type 1 and 2:
=General clotting defect symptoms e.g Epistaxsis
Type 3:
=Spontaneous severe bleeding
What haematological issues can be caused by Liver disease?
Liver produces the clotting factors, prothrombin and fibrinogen
=Thrombocytopenia
=Abnormal coagulation (more bleeding)
A patient is deficient in Vitamin K due to their Irritable Bowel Disease. What coagulation results would you expect?
Increased APTT and Prothrombin time
What are the causes of Vitamin K deficiency?
-Drugs (anticoagulants e.g Warafin)
-Malnutrition (lack of green leafy veg, alcoholism)
-Malabsorption (IBD, Gall stones etc)
What does Thrombophilia mean?
INCREASE OF CLOTTING
What is Disseminated Intravascular Coagulation (DIC)?
Severe life threatening Thrombophillia triggered by illness:
-Severe Septicaemia (Meningococcal, E.coli)
-Haematological malignancies and tumours
-Severe burns or trauma
-Obstetric complications
What is the management of Disseminated Intravascular Coagulation (DIC)?
Severe–>Blood transfusions
Non-symptomatic–>LMW Heparin
What are the 3 inherited thrombophilia disorders to know?
1.Factor V Leiden (FVL)
2.Antithrombin (AT) deficiency
3.Protein C and S Deficiency
What is Antiphospholipid Coagulation disorder?
Autoimmune condition characterised by recurrent thrombosis, obstetric complications.
A patient with recurrent thrombosis has a blood test. What antibody could point towards the cause?
Antiphospholipid Antibodies (APAbs)
=Antiphospholipid syndrome (APS)
What is the management for Antiphospholipid syndrome (APS)?
Lifelong anticoagulation therapy:
-Warafin
During pregnancy:
Aspirin and LMW Heparin
What coagaulation results would you expect from a patient with Disseminated Intravascular Coagulation (DIC)?
Increased PT, Bleeding time and APTT
What is a general definition of Leukaemia?
Abnormal proliferation of leucocytes and their precursors in the bone marrow and peripheral blood which is classified either as MYELOID (WBCs e.g Neutrophils, Basophils etc) or LYMPHOID dependant on what WBC is affected.
What are the 4 types of Leukaemias?
1.Acute Myeloid Leukaemia (AML)
2.Acute Lymphoblastic Leukaemia (ALL)
3.Chronic Myeloid Leukaemia (CML)
4.Chronic Lymphocytic Leukaemia (CLL)
What is the mean age of onset for Acute Myeloid Leukaemia ?
Equal proportion before and after 60 BUT MEN ARE MORE FREQUENTLY AFFECTED AFTER 60
What is the genetic characteristic of Acute Myeloid Leukaemia?
Chromosomal translocation t(15:17)
What is the most common complication of Acute Myeloid Leukaemia?
DIC (Disseminated Intravascular Coagulation)
A patient with known Acute Myeloid Leukaemia presents to the ER with excessive and prolonged bleeding as well as chest pains and low BP. What could this be and what should be done?
Most likely to be Disseminated Intravascular Coagulation (hypercoagulability disorder associated with AML)
What are the symptoms of Disseminated Intravascular Coagulation?
-Bleeding, from many sites in the body.
-Blood clots.
-Bruising.
-Drop in blood pressure.
-Shortness of breath.
-Confusion, memory loss or change of behavior.
-Fever.
What is the presentation of Acute Myeloid Leukaemia?
1.Anaemia
=Fatigue and Breathlessness
2.Neutropenia
=Recurrent infections
3.Thrombocytopenia
=Bleeding, Bruising and Petechiae
What is Neutropenia and how does it present?
Low Neutrophils in the blood presents as RECURRENT INFECTIONS
What is Petechiae and what does it indicate?
Pinpoint, round spots that form on the skin and can cluster into a rash.
They’re caused by bleeding i.e Thrombocytopenia and other coagulation pathologies
What symptoms of a patient with Acute Lymphoid Leukaemia indicate end-organ infiltration?
1.Liver and spleen
=Hepatomegaly and Splenomegaly
2.Gums
=Gingivitis (inflammation of the gums) and bleeding
What is the gold standard for diagnosing Acute Myeloid Leukaemia?
Bone Marrow Autopsy and Aspiration
=More blast cells and AUER RODS present
A patient has suspected Acute Myeloid Leukaemia. What investigations are necessary?
-Bloods and film
-Bone marrow biopsy /aspiration
-Cytogenic Analysis (to guide treatment plan)
What is Tumour Lysis syndrome?
Group of metabolic disturbances which commonly occur as a result of CHEMOTHERAPY :
1.Hyperuricaemia
2.Hyperkalaemia
3.Hyperphosphataemia
4.Hypocalcaemia
–>Renal failure
What is Neutropenic Sepsis?
An oncology emergency seen in patients undergoing Chemotherapy or with underlying haematological malignancy
How does NICE define Neutropenic Sepsis?
Neutrophil count is <0.5 x 10^9 /L with fever
What should be done within 1 hour of Sepsis diagnosis?
Give 3, Take 3
GIVE:
1.Oxygen
2.IV fluids
3.Antibiotics
TAKE:
1.Blood cultures
2.Lactate, FBC
3.Urine output
What antibiotics are given for Neutropenic Sepsis?
IV Piperacillin-Tazobactam (Tazocin)
What steps to ensure correct breathing should be done for a patient with Neutropenic Sepsis?
1.High flow O2
2.Give nebuliser (0.9% saline or Salbutamol)
3.ABG
4.CXR if chest infection seems to be the cause
A patient has Acute Myeloid Leukaemia. What type of Tumour Lysis syndrome should be actively avoided and how is that done?
Hyperuricaemia
=Allopurinol / Rasburicase given as well as advising for adequate hydration
What Chemotherapy agent is commonly used for Acute Myeloid Leukaemia?
Cytarabine
What prophylactic antibody is usually prescribed for a patient with Acute Myeloid Leukaemia?
Fluoroquinolone
What type of myeloid cells are usually affect in Acute Lymphoblastic Leukaemia (ALL)?
B cells (80%) rather than T cells (20%)
What is the usual age of onset for Acute Lymphoblastic Leukaemia?
Most under the age of 6 (75% if cases)
What illness does Acute Lymphoblastic Leukaemia have a strong association with?
Down’s Syndrome aka Trisomy 21
Between Myeloid and Lymphoblastic Leukaemia, what is most likely to cause CNS involvement and therefore symptoms such as headaches and neck stiffness?
Lymphoid since lymphocytes pass more readily through the BBB than Myeloids
What are the symptoms of Acute Lymphoblastic Leukaemia?
1.Fatigue and malaise (usual first symptoms)
2.Anaemia, Recurrent infections and bleeding
3.Infiltrative symptoms
-Thymic mass
-Splenomegaly (with or without pain)
-Pupura and Gingival hypertrophy (from the bleeding)
-Testicular enlargement
-CNS symptoms - Headaches and neck stiffness
What is the gold standard for diagnosing Acute Lymphoblastic Leukaemia?
Blood film / Bone marrow biopsy
=more lymphoblasts
How would you test for CNS involvement in a patient with Acute Lymphoblastic Leukaemia?
Lumbar Puncture for CSF Cytology and Flow Cytometry
What would be given to a patient with Acute Lymphoblastic Leukaemia to reduce CNS involvement?
Prophylactic Intra-thecal therapy
What is the common age of onset for Chronic Myeloid Leukaemia?
Predominantly the elderly (over 55yrs)
What gene is affected in Chronic Myeloid Leukaemia?
BCR-ABL
What are the symptoms of Chronic Myeloid Leukaemia?
Slow (insidious) onset of:
-fatigue
-night sweats
-weight loss
-unspecific abdominal discomfort
A patient has suspect Leukaemia and their blood results are:
-Decreased Hb and Platelets
-Increased White Blood Cells
What types of Leukaemia could this be?
1.Acute Myeloid Leukaemia
2.Acute Lymphoblastic Leukaemia
3.Chronic Myeloid Leukaemia
For Chronic Myeloid Leukaemia, what blood test results would you expect?
Increase in White blood cells and PLATELETS
What is seen on a blood film and Bone Marrow Autopsy from a patient with Chronic Myeloid Leukaemia?
Elevated neutrophils
What analysis confirms the genetic issue that caused Chronic Myeloid Leukaemia?
Cytogenic Analysis
=Reveals Philadelphia Chromosomal abnormality t(9:22)
What is the main management of Chronic Myeloid Leukaemia?
Tyrosine Kinase Inhibitors:
=Imatinib
What is the most common Leukaemia in the west?
Chronic Lymphocytic Leukaemia (CLL)
What is the usual group of people to have Chronic Myeloid Leukaemia?
MALES predominate (i.e twice as likely to get it compared with females)
What are the general symptoms of Leukaemias?
Insidious (slow) onset with symptoms such as fatigue, night sweats and then anaemia, hepatomegaly and splenomegaly.
What factor significantly decreases a patient’s prognosis (to 5years life expectancy)?
If Anaemia is present (as well as low platelets)
What is the gold standard of diagnosing Chronic Myeloid Leukaemia?
Blood film = Fragile Lymphocytes
What tests are required for diagnosing Chronic Myeloid Leukaemia?
-Blood smear/film
-Lymph node biopsy
-Immunophenotyping
What Leukaemia does not require a Bone Marrow Biopsy?
Chronic Myeloid Leukaemia
What is a major risk factor if Hodgkin Lymphoma?
Epstein Baar Virus
=seems to trigger abnormal B cell uncontrolled poliferation
What testing is required to diagnose Hodgkin’s Lymphoma?
1.Pan-CT of the Neck
=to assess for lymphadenopathy
2.Lymph node biopsy
Others:
-FBC, U&E, LFT and Blood film
What would you expect to see in a patient’s blood film if they had Hodgkin’s Lymphoma?
Reed-Sternberg cells
What is the curative treatment option for Hodgkin’s Lymphoma?
Chemo-radiotherapy
What group is more likely to have Non-Hodgkin Lymphoma?
MALES get it more than females
65-75yrs
What are the 3 strongly associated illnesses with Burkitt Lymphoma?
-Epstein Baar Virus
-Chronic Malaria
-AIDs
What testing should be done for suspected Non Hodgkin’s Lymphoma?
-Blood film and baseline bloods
-Lymph Node Biopsy
(GOLD STANDARD)
-PET-CT scanning
-Bone marrow biopsy / aspirate
What treatment is recommended for symptomatic Non Hodgkin’s Lymphoma?
Chemotherapy in combo with Rituximab
What treatment is recommended for asymptomatic Non Hodgkin’s Lymphoma?
Radiotherapy
What is Meltzer’s triad?
The 3 symptoms for Cryoglobinaemia
1.Pupura
2.Weakness
3.Arthralgia (joint stiffness)
What is Cryoglobinaemia?
Cryoglobulins present which produce IgM antibodies and malignant B cells.
Who does Multiple Myeloma affect most?
Males more than females and more common in Afro-Caribbeans with average onset of 63-70
What are the main clinical symptoms of Multiple Myeloma?
-Fatigue due to anaemia
-Bony pain (usually back)
What emergencies / other issues can indicate Multiple Myeloma?
-Pathologic fractures
-Hypercalcaemia
-Recurrent bacterial infections (Sepsis)
-Proteinuria / Dehydration due to Renal Impairment
What would be present in a patient with Multiple Myeloma’s serum protein electrophoresis and what would be done next?
Gamma Paraproteins
+Serum Immunofixation (to identify the type of paraprotein - IgA, IgD, IgE, IgM etc)
What tests are required to diagnose Multiple Myeloma?
-Bloods
-Serum electrophoresis
-Bone marrow biopsy /aspirate
-Skeletal imaging - MRI / PET/CT
What immuno/chemotherapy should be given to a patient with Multiple Myeloma?
Proteasome inhibitor:
-Bortezomib + Cyclophosphamide + Dexamethasone
What is the average age of onset of Polycythaemia Vera (PV)?
Over 60yrs (predominantly seen in the elderly)
What is Hyperviscosity Syndrome?
Due to high cell counts:
-End organ congestion:
1.Visual disturbances
2.Neurological symptoms (headaches, dizziness)
3.Cardiac (angina and dyspnoea)
-Reduced blood flow:
1.Recurrent thrombosis
2.Bleeding
What are the symptoms of Polycythaemia Vera (PV)?
-Hyperviscosity syndrome
-Pruritus
<5% have acute burning and erythema of the hands
What results would you expect from a blood test from a patient with Polycythaemia Vera (PV)?
Normocytic, normochromic anaemia
What results would you expect from a U&E from a patient with Polycythaemia Vera (PV)?
Increased Calcium, ALP and ESR
What mutation causes Polycythaemia Vera (PV)?
JAK2 (tyrosine kinase protein)
What does an elevated D-dimer mean?
D-dimer is a fibrin degradation product which is elevated in the presence of blood clots.
In lead poisoning, where does the Lead accumulate?
In the metaphysis of the bones which shows up as bands of increased density on x-ray which can aid in the diagnosis of lead poisoning
What type of anaemia does Lead poisoning cause?
Hypochromic Microcytic Anaemia
What Granulocyte-colony Stimulating factors are given to a patient with Neutropenic Sepsis.
Filgrastim
Perfilgrastim
What drugs are given to increase Leukocyte count (specifically Neutrophils) during Neutropenic Sepsis?
Granulocyte-colony Stimulating factors
In renal failure what drug is given to a patient to treat anaemia (thats caused by the RF)?
Darbepoetin (EPO analog)
A 2 year old patient presents with recurrent infections. What immunoglobulin deficiency seems most likely?
IgA
=Most common deficiency as well as IgA being PRESENT IN BREAST MILK
-therefore symptoms usually will start after the end of breast milk feeding
IgA deficiency would most likely cause what type of infections?
Gastric
-IgA is the main immunoglobulin that protects the GI tract
What type of haematological pathology are patients with Down’s Syndrome at an increased risk of?
Leukaemias
What type of Leukaemia is treated with All-trans retinoic acid (ATRA)?
Acute promyelocytic leukaemia (APML)
A patient has Acute promyelocytic leukaemia. What genetic abnormality would they have?
t(8:21) or t(15:17)
What is the pathophysiology of Thrombotic Thrombocytopenia Purpura?
Autoimmune disorder where autoantibodies destroy the enzyme responsible for cleaving Von Willebrand Factor to activate it. VWF is responsible for clotting.
What is the gold star diagnostic for Paroxysmal Nocturnal Haemoglobinuria (PNH)?
Flow cytometry
= CD55 and CD59 negative red and blood cells.
Describe the presentation of Paroxysmal Nocturnal Haemoglobinuria (PNH)?
-Haematuria
-Symptoms of anemia.
-Venous thrombosis is also a common occurrence.
What does Atopy mean?
Genetic tendency to have a heightened immune response e.g Eczema
A patient has suspected Disseminated Intravascular Coagulation. What would you expect from their blood film?
Schistocytes
What results would you expect from investigations into suspected Disseminated Intravascular Coagulation?
Can be variable but typically: 1.Prolonged coagulation times
2.Thrombocytopenia
3.High levels of fibrin degradation products (FDPs)
4. Elevated D-dimer levels, 5.Microangiopathic pathology (Schistocytes) on peripheral smears are suggestive findings.
What tests should be done for a patient with suspected Sickle Cell Anaemia and what would be the results??
-Peripheral blood smear
=High RETICULOCYTES and Sickle cells present
-Solubility test
-Haemoglobin Electrophoresis
*DIAGNOSTIC: HbS with no HbA
-U&Es, LFTs
What is the gold standard diagnostic for Sickle Cell Anaemia ?
Haemoglobin Electrophoresis
=HbS with no HbA
Where do T cells mature?
Thymus
A patient has scrotal cancer. What lymph node can therefore be vulnerable to metastasis (think about lymph drainage)?
Superficial inguinal lymph nodes
A patient has cancer of the Penis. What lymph node can therefore be vulnerable to metastasis (think about lymph drainage)?
Deep inguinal lymph nodes
A patient has cancer of the Testes. What lymph node can therefore be vulnerable to metastasis (think about lymph drainage)?
Para-aortic lymph nodes
A patient has cancer of the Anal canal (above the pectinate line). What lymph node can therefore be vulnerable to metastasis (think about lymph drainage)?
Internal iliac lymph nodes
A patient has cancer of the Descending colon. What lymph node can therefore be vulnerable to metastasis (think about lymph drainage)?
Inferior mesenteric lymph nodes
What additional symptoms to Sideroblastic Anaemia, can Chronic Lead Poisoning present?
+Neurocognitive impairment
+Burton’s lines (blue lines on gums)
Note: Lead poisoning can be seperate and not cause Sideroblastic anaemia
What is Acute Porphyrias?
Group of disorders resulting from defects in haem synthesis
What are the symptoms of Acute Porphyrias?
Abdominal pain (general)
Nausea
Confusion
Hypertension
Peripheral Neuropathy
What is the investigative diagnostic of Acute Porphyrias?
Urinary porphobilinogen level
What is the treatment for Acute Porphyrias?
Supportive:
IV Haem Arginate
What is the inheritance of sickle cell disease?
Autosomal recessive
What is the presentation of a patient with Hypercalcaemia?
-Constipation
-Polyuria
-Low mood
Describe a typical presentation of Sickle cell anaemia.
If not detected at birth:
-Progressive anaemia
Exacerbation of symptoms by cold weather and exercise
-Aches and pains (vaso-occlusive crisis)
What is the most common acute presentation of sickle cell disease?
Vaso-occlusive crisis
What would you expect the total iron binding capacity to be for a patient with iron deficient anaemia?
High
=lack of iron doesn’t impact the iron’s affinity
What would you expect the total binding capacity and ferritin to be for a patient with Anaemia of Chronic disease?
Low TIBC and high ferritin
What is Anaemia of Chronic Disease?
Anaemia caused by long standing illnesses such as malignancy, chronic infection etc
What is Non-infective leucocytosis?
Increased number of white blood cells (which is not harmful or indicative of pathology)
List the causes of Non-infective leucocytosis.
-Medications:
-lithium
-corticosteroids
-beta-agonists (e.g Salbutamol)
-Excessive physical or emotional stress (such as fever, injury or surgery).
Burns.
-Autoimmune disorders:
-Lupus
-Rheumatoid arthritis.
-Thyroid problems.
-Dental caries (cavities).
List the complications of a Splenectomy.
Vulnerable to infections
e.g Pneumococcal sepsis, Meningitis, Influenza)
-due to reduced immune response with the absence of a spleen
Describe the presentation of Reactive Lymphadenopathy.
-Tender Lymphadenopathy with associated symptoms:
(Fever, Malaise, Fatigue and Sore throat)
Describe the lymph node observations of a Lymphoma.
Nontender rubbery lymph node in the neck
Although it is difficult to differentiate between Non- and Hodgkin’s Lymphoma, what are the key differentiators to remember?
Onset :
-Non: Present in all ages
-Hodgkin’s : Typically present in young men
Exacerbating factors:
!Typical feature of hodgkins (non non-hodgkin’s) is exacerbation of symptoms after drinking alcohol(
How does Oesophageal varices affect the spleen and platelet count?
-Splenomegaly
-Thrombocytopenia (enlarged spleen increases the sequestration of platelets to the spleen decreasing circulating platelet levels)
