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147 Cards in this Set
- Front
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Three mechanisms that cause Anaemia |
Breakdown (Haemolysis) Decreased production Sequestration in the spleen (Hypersplenism) |
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Symptoms of Anaemia |
Tiredness, decreased exercise tolerance, SOBOE, palpitations, headaches |
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Signs of Anaemia (remember the difference between symptoms and signs!) |
Tachycardia Heart Murmurs Retinopathy (if long term) |
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What are some common causes of Anaemia? |
Iron deficiency B12/Folate deficiency Chronic Disease Bleeding Bone Marrow Infiltration Autoimmune Haemolytic Anaemia |
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What are some causes of Microcytic Anaemia? |
Remember the big three: Iron Deficiency Thalassemia Anaemia of Chronic Disease Then you have the others Myelodysplasia Lead Poisoning |
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What is the daily requirement of iron for Men? |
1mg |
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What is the daily Iron requirement for premenopausal women? |
2mg |
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What are some causes of Iron Deficiency? |
Dietary lack Malabsorption Increased demand Increased loss |
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What are symptoms of Iron Deficiency? |
Anaemia symptoms listed previously + Painful mouth Dysphagia Pica Increased infections Impaired growth
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What are some signs of Iron Deficiency? |
Glossitis Blue Sclera Angular Stomatitis Koilonychia (spoon nails) |
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In Iron deficiency, what would be the findings on a blood film? |
Smaller, lighter RBCs (microcytic, hypochromic anaemia), poikilocytes (pencil cells), target cells, increased platelets |
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What would be the results from iron studies in iron deficiency? (Ferritin, Serum Iron, Iron Saturation, Transferrin) |
Ferritin, Serum Iron and Saturation goes down, Transferrin goes up |
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Upon suspicion of Iron Deficiency, what are some important points to investigate in history? |
Menstrual history, GIT abnormalities, obvious bleeds. Basically, BLEEDS. Remember, always try to find the CAUSE of the iron deficiency. Don't want to get screwed over in court if you don't. |
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What are some causes of Macrocytic Anaemia? |
B12 and/or Folate deficiency, Drugs (causes of Megaloblastic Anaemia) Newborns Alcoholism, liver disease Hypothyroidism Haemolysis Marrow Disorders And of course, Idiopathic |
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What does the Anaemia of Chronic Disease look like on a blood film? |
Hypochromic, Normocytic anaemia |
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How can you distinguish between Anaemia of Chronic Disease and other anaemias? |
History Blood Film Anaemia of Chronic Disease tends to be less severe |
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What is Anaemia of Chronic Disease associated with? |
Infection Chronic Inflammation Cancer |
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Describe the pathogenesis of the Anaemia of Chronic Disease |
Decreased RBC survival Decreased EPO secretion Decreased marrow response to EPO Iron limited Erythropoiesis |
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What are some clinical features of Megaloblastic Anaemia? |
Angular Stomatitis, Glossitis, Anaemia, Purpura, Infection, Jaundice, Malabsorption and thus weight loss |
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What will a Blood Film reveal in Megaloblastic Anaemia? |
Macrocytosis Neutropenia Hypersegmented Neutrophils Thrombocytopenia Oval Macrophages |
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What other investigations (other than a FBC and Blood Film) would you order for investigation of Megaloblastic Anaemia? |
Serum B12 and Folate Bone Marrow Aspirate |
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Why might a Cervical Smear look abnormal in Megaloblastic Anaemia? |
B12 and Folate are needed for DNA replication, so in deficiency, any replicating cells will be affected. |
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Where in the bowel is Folate absorbed? |
Proximal Small Bowel |
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What are some common causes of Folate Deficiency? |
Pregnancy Decreased intake (Food faddism, cooking, chronic illness, alcohol, poverty) Increased cell proliferation Malabsorption (esp Coeliac disease) Drugs (anticonvulsants, OCP, antibiotics, methotrexate) |
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Where in the bowel is B12 absorbed? |
Terminal Ileum |
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What are some common causes of B12 deficiency? |
Pernicious anaemia Veganism Gastrectomy Intestinal disorders |
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What investigations would you order if you suspect B12 deficiency? |
FBC Serum B12 Intrinsic Factor Antibodies |
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In Haemolytic Anaemia, what will you see on investigation? |
Signs of RBC breakdown, so: Anaemia Increased bilirubin Increased LDH Decreased Haptoglobin Also signs of increased RBC production: Reticulocytes Marrow Hyperplasia |
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(I found this useful to know) What is Haptoglobin? |
Protein in the blood that binds to free Haemoglobin outside RBCs |
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What measure is used to determine Haemolytic Anaemia? |
Urinary Haemosiderin |
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What are the two divisions of the causes of Haemolytic Anaemia? |
Intravascular Extravascular |
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What are the Extravascular causes of Haemolytic Anaemia further divided into? |
Spherocytic and Non-spherocytic anaemia |
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What is the normal composition of Adult Bone Marrow? |
50% Haematopoietic tissue and 50% fat |
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What are 3 potential problems with the bone marrow? |
Anaplastic Anaemia Leukaemia infiltrating the bone marrow Toxicity destroying the marrow (surely there are more but these re 3 from the notes) |
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Differential Diagnosis for Pancytopenia? |
Anaplastic Anaemia, Bone Marrow Infiltration, Myelodysplasia, Megaloblastic Anaemia, Hypersplenism, Miscelaneous e.g. alcohol, infection |
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What will a Bone Marrow aspirate reveal in Anaplastic anaemia? |
fat cells of the Bone Marrow, but no haematopoietic tissue |
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What may cause Anaplastic Anaemia? |
An intrinsic defect in the stem cells (either they are dysfunctional, or have reduced production) Extrinsic damage to stem cells (immune or toxins) Most common: idiopathic (most likely immune) or drugs |
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Why is Anaplastic Anaemia a medical emergency? |
Can get infection (reduced WBC) or die from bleeding (thrombocytopenia) |
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How do you manage a patient with Anaplastic Anaemia? |
ADMIT Give Antibiotics within 1 hour of admission Give platelets and RBC transfusion If cause is immune, immunosuppress If younger: consider stem cell transplant If older: the problems are co-morbidities, and Graft Vs Host disease (more common in elderly) |
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What are Haematopoietic Stem Cells? |
Multipotent cells residing in the bone marrow. Can form any of the blood cell lineages, depending on the cytokines they are exposed to. Only viable in bone marrow, and have the power of self renewal in the bone marrow |
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Name some Haematopoietic cytokines (don't think these are really too important. Wouldn't spend too much time on them) |
EPO Thrombopoietin G-CSF (neutrophil production) GM-CSF Stem cell factor IL3 |
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In what clinical events are Acute Phase Reactant levels altered? |
Infection Malignancy Inflammatory state Tissue injury |
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Which acute phase reactants increase in infection, malignancy, inflammation or injury? |
Fibrinogen, Haptoglobin (decreases in haemolytic anaemia), CRP, vWF, complement, Factor VIII, Ferritin |
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Which acute phase reactants decrease in infection, malignancy, inflammation or injury? |
Albumin Prealbumin Transferrin |
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What are 2 commonly used investigations that test for Acute Phase Reactants? |
ESR and CRP |
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When is the ESR test used? |
Diagnostic aid in uncertain circumstances For monitoring specific diseases e.g. Temporal Arteritis, Polymyalgia Rheumatica, Rheumatoid Arthritis NOT used as an asymptomatic screen
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What are the limitations of the ESR? |
Will increase the faster the RBC drop Will increase with Rouleaux effect |
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Describe the C Reactive Protein |
Synthesized in the liver Part of the Innate Immune System Binds to surface of dying cells and bacteria, activating compliment for phagocytosis Rises within 6 hours after the stimulus No diurnal variation or effect from drugs |
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When is the CRP test used? |
To monitor patients at risk of infection |
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What are some causes of Neutrophilia? |
Inflammation, Cancer, Blood Disorders, Infections, Acute bleeding, Acute Haemolysis, Physiological |
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What feature on blood film indicates infection? |
Left Shift |
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Describe the toxic changes in Neutrophils |
Increased granules Increased Vacuoles Dohle bodies Nuclear clumping Occur due to switch to protein synthesis |
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What is Virchow's Triad? |
Triad of changes causing increased risk of thrombosis Changes to Blood Changes to Blood Vessels Changes to Flow |
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What are some causes of change in blood? |
Decreased Fibrinolysis Increased vWF, Factor VIII, Fibrinogen |
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What are some causes of change in blood flow? |
Surgery Immobilization Anaesthesia Local Pressure
e.g.velocity is reduced when standing and further on sitting. Sitting also increases pressure the popliteal fossa |
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What are some causes of change in vessel wall? |
Burns Endotoxin Hypoxia Direct trauma |
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What are signs of Venous Thromboembolism in the leg? |
Redness, swelling, tenderness, dilated veins |
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What are the more common causes of primary (inherited) hypercoagulable state? |
Factor V leiden, Prothrombin Gene Mutations |
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What are some causes of secondary hypercoagulable state? |
Malignancy, Pregnancy, Surgery, Trauma, Stasis, Myeloproliferative Disorders, Antiphospholipid disorders, Age, Dehydration => Viscosity, Drugs |
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Janine, 63, is flying from Auckland to San Francisco in December. What risk factors for Venous Thrombosis will you look for in her before she departs |
Hormonal Therapy (increased Oestrogen causes slight hypercoagulable state), Surgery, Malignancy, Immobilization, Obesity, Previous VTE, Significant family history, Pregnancy (unlikely in this patient) |
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Janine, 63, is flying from Auckland to San Francisco in December. What will protect her from VTE onboard her flight? |
Aisle Seats Compression Stockings |
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Janine, 63, is flying from Auckland to San Francisco in December. She asks you about using Aspirin for VTE prophylaxis, because she saw it on a forum website on Google. What will you tell her? |
Aspirin is not such a good idea: Increased risk of upper GI bleeding. LMWH a better drug (but of course you aren't going to jump straight to meds before anything else and if she is not particularly concerning) |
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Describe Polycythaemia |
An increase in total RBC mass Can be spurius: an example is dehydration |
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How does Polycythaemia lead to an increase in Thrombosis risk? |
increased haematocrit therefore increased blood viscosity |
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What causes primary Polycythaemia? |
Myelodysplasia |
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What causes secondary Polycythaemia? |
Driven by EPO metabolism, anything that lowers O2 concentration. Causes can be normoxic (renal diseases e.g. RCC, renal stenosis, liver disease, tumors, esp. posterior cerebellar tumors) or hypoxic (high altitude, pulmonary disease, abnormal Hb, cyanotic heart disease, hypoventilation syndromes) |
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What are symptoms of Polycythaemia rubra vera? |
Headache, weakness, pruritis, dizziness, sweating |
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What are signs of Polycythaemia rubra vera? |
Hepatosplenomegaly, flushed appearence, skin and conjunctival plethora |
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What will investigation produce in Polycythaemia rubra vera? |
Low EPO High RBC, neutrophils, platelets, Hb Hypercellular Bone Marrow |
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Most common cause of death in Polycythaemia Rubra Vera is... |
thrombotic event |
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How would you treat someone with Polycythaemia Rubra Vera? |
Phlebotomy, Anti-platelet agents, Marrow suppressing agents |
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What genetic mutation causes polycythaemia rubra vera? (doubt this is important) |
JAK2 gain of function. Codes for tyrosine kinase signal trandsucer for EPO receptors |
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What causes Iron Overload? |
Haemochromatosis, transfusion |
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Describe the genetics of Haemochromatosis |
Variable penetrance C282Y (most common and potent), and H63D (doubt these are important) |
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What organs does Iron Overload affect? |
Liver: cirrhosis and hepatocellular cancer Pancreas: Diabetes Joints Testes Heart Skin |
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What would the results of blood tests look like in Iron Overload? |
High Ferritin Fasting transferrin saturation over 45% |
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What further investigations would you order for Iron Overload? |
Liver Biopsy and Quantitative Fe MRI |
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How do you treat Iron Overload? |
Phlebotomy |
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What are Myeloproliferative disorders? |
A primary clonal proliferation of Myeloid cells, that can affect any of the three cell lineages. |
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What is the most common cause of Myeloproliferative disorders in outpatients? |
Iron deficiency |
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When are increased platelets most commonly seen? |
After Surgery or Trauma |
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What does Leukoerythroblastosis imply? |
Disturbance of the blood/marrow barrier |
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What do you see on blood film in Leukoerythroblastosis? |
Nucleated RBCs and immature neutrophils |
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What are some causes of Leukoerythroblastosis? |
Immaturity of bone marrow, toxicity, hypoxia, mechanical damage, tumor, septicaemia, respiratory failure, haemolysis, extramedullary haematopoiesis |
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What is Extramedullary Haematopoiesis? |
Making cells outside the bone marrow (no blood marrow border). Common in myeloproliferative disorders, especially Myelofibrosis. |
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What are common sites for Extramedullary Haematopoiesis? |
Spleen, Liver. There is always splenomegaly. |
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What are symptoms in Chronic Granulocytic Leukaemia? |
Fatigue, bleeding, weight loss, splenomegaly. May be an incidental finding. |
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What would be the blood count, bone marrow aspirate and biochemistry results in Chronic Granulocytic Leukaemia? |
High WBC. Anaemia, High platelets, Hyperplastic Bone Marrow full of WBCs High Uric Acid due to high cell turnover |
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What mutation is Chronic Granulocytic Leukaemia associated with? |
Philadelphia Translocation (Reciprocal 9:22 translocation) |
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How would you treat Chronic Granulocytic Leukaemia? |
Hydroxyurea (slows time course but doesn't cure) and imatinab Other options: Interferon Bone Marrow Transplant |
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Describe the progression of Chronic Granulocytic Leukaemia. |
Three phases: Chronic, Accelerated, Blast Transformation (blast transformation is acutely aggressive and rapidly fatal) Time course is usually around 3 years |
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Describe Chronic Idiopathic Myelofibrosis |
Slow onset condition, in which marrow fills up with Collagen and Scar tissue
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30% of cases of Chronic Idiopathic Myelofibrosis are preceded by... |
Polycythaemia vera |
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Describe the signs and symptoms of Chronic Idiopathic Myelofibrosis |
Anaemia symptoms Weight Loss Night Sweats Massive Hepatosplenomegaly, causing problems e.g. early satiety Splenic infarcts causing lots of pain |
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There is massive splenomegaly and painful splenic infarcts in Chronic Idiopathic Myelofibrosis. How can we reduce the size of the spleen? |
Surgery, radiotherapy, or chemotherapy |
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What are findings on blood count, blood film and bone marrow aspirate in Chronic idiopathic myelofibrosis? |
Anaemia, WBC and platelets high early and low late Tear drop RBCs Collagen fibrosis in bone marrow |
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How do you treat Chronic idiopathic myelofibrosis? |
Observation, Chemotherapy, Splenectomy if symptomatic, stem cell transplant if young and chance of a cure |
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What is the mean survival time for Chronic idiopathic myelofibrosis? |
3-4 years |
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10% of patients with Chronic Idiopathic Myelofibrosis go on to develop... |
Acute Leukaemia |
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In what age group is Essential Thrombocytopenia most common? |
Elderly, but seen in all age groups |
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Describe Thrombocytopenia |
Higher than normal Platelet count. Cause is either primary or secondary |
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What are some primary causes of Thrombocytopenia? |
Essential Thrombocytopenia Another Myeloproliferative disorder MUST DETERMINE IF THROMBOCYTOPENIA IS PRIMARY OR SECONDARY |
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What are some secondary causes of Thrombocytopenia? |
Generally indicates reactive process Iron Deficiency Anaemia Haemorrhage Trauma Malignancy Inflammation Post-splenectomy
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What does Bone Marrow aspirate reveal in Essential Thrombocytopenia? |
Increased numbers of enlarged, mature, megakaryocytes. |
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What are some symptoms and signs of Essential Thrombocytopenia? |
Often Asymptomatic Patients can present with bleeding (dysfunctional platelets), thrombosis, or splenomegaly (can be similar to presenting symptoms and signs of Polycythemia Vera) |
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What is revealed on blood count and blood film in Essential Thrombocytopenia? |
Increased platelets, abnormal platelet morphology and function (PFA100), normal or mild increase in WBC, normal or mild iron deficiency anaemia |
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How do you treat Essential Thrombocytopenia? |
Observation, Aspirin (decrease risk of thrombosis), Anagrilide and Hydroxyurea (decreasing platelet count), Interferon |
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What does Haemostasis involve? |
It is stopped bleeding. Involves Vasoconstriction, platelet activation and activation of coagulation cascade, leading to conversion of fibrinogen to fibrin. |
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Define Blood Coagulation |
conversion of Soluble Fibrinogen to Insoluble Fibrin |
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What is the lab test for the intrinsic system of the Coag Cascade? |
APTT |
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What is the lab test for the extrinsic system of the Coag Cascade? |
PT/INR |
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What is Thrombin time useful for? |
Monitoring Dabigatran |
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Which factor converts fibrin to cross-linked fibrin? |
XIIIa |
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What are some acquired disorders of coagulation? |
liver disease, DIC, VitK deficiency, Uraemia, Massive blood transfusion, factor inhibitors |
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What are some congenital disorders of coagulation? |
Haemophilia A and B, von Willibrand disease. Can get other factor deficiencies but these are extremely rare. |
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What is the role of the liver in Coagulation? |
Synthesizes a number of coagulation factors, inhibitors, fibrinolytics and carboxylases. REMEMBER VITK |
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What is the end result of DIC? |
conversion of large amounts of fibrinogen to fibrin |
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Describe the three pathways that lead to DIC |
Release of tissue Thromboplastin in the vasculature, through trauma, malignancy or major surgery. Activation of Factor XII in endothelium, occuring in sepsis, burns, anoxia and acidosis Activation of either factor X or II which occurs in pancreatitis or amnionic fluid emboli |
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How dies DIC cause organ damage? Which organs are most susceptible to this? |
In DIC, get fibrin deposition in microvasculature and then you get clotting and ischaemic organ damage. Kidneys and brain are susceptible to this. |
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How does DIC cause microangiographic haemolytic anaemia? |
Fibrin cross-stranding shreds RBCs causing microangiopathic haemolytic anaemia |
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What will be the result of Blood Tests in DIC? |
INR and APTT increased, Fibrinogen and Platelets decreased, FDPs increased (D-dimer) |
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How do you manage a patient with DIC? |
TREAT THE CAUSE In the meantime, give platelet transfusion, fresh frozen plasma and cryoprecipitate |
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What are some causes of Vitamin K deficiency? |
Haemorrhagic disease in newborns, Dietary deficiency, Biliary obstruction (because fat soluble vitamin), Malabsorption, Liver disease, Warfarin, VVitamin E, antibiotics, hyantoids |
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How does Renal Failure affect Haemostasis? |
causes defective platelets (somehow - PFA100 is prolonged) Severity of coagulopathy correlates with severity of renal failure |
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How do you treat Haemostasis issues due to Renal Failure? |
RBC transfusion, Vasopressin |
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How does a massive blood transfusion cause coagulopathy? |
Only replacing RBCs, not factors, which get diluted. |
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How do you treat coagulopathy due to Massive Blood Transfusion? |
Give platelets, fibrinogen and FFP |
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What are factor inhibitors? |
Autoantibodies to factors, usually FVIII or FIX |
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How do you distinguish between simple factor deficiency and an inhibitor? (very important to do this) |
Do a 1:1 mix. If the coagulopathy corrects, it is a factor deficiency. If not, it is an inhibitor |
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A 14 year old girl comes in with easy bruising. Her APTT is elevated, PFR100 low-ish. What do you suspect? |
von Willebrand's disease. Do a von WIllebrand screen |
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A 14 year old girl comes in with easy bruising. Her APTT is elevated. PFR is fine. What do you do to further investigate? |
Suspect Haemophilia. Test F VIII THEN F IX if VIII is negative(VIII is more common) If still negative, start testing the other factors, cos this is going to be a rare one. When you find the problem factor, do a 1:1 mix, to check for inhibitors |
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What is Tranexamic Acid? |
Antifibrinolytic. Blocks antithrombin |
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How do you treat someone bleeding and having inhibitors, to Factor VIII? |
Give infusion of F VIIa |
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What is the most common form of adult leukemia? |
Chronic Lymphoid Leukaemia. Does not require urgent treatment |
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How is Leukaemia categorized? |
Acute or Chronic. Further divided into Granulocytic and Lymphocytic |
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What is the clinical course for Acute Leukaemia? |
Rapid onset, rapid demise if not treated |
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What are the symptoms caused by in Acute leukaemia? |
Either marrow failure or tissue infiltration |
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What other thing associated with Cancers can cause marrow failure and tissue infiltration? |
Chemotherapy. More of an issue in chronic cases |
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What are the signs of Acute Leukaemia? |
Anaemia, bleeding, infection (from pancytopenia due to marrow failure) Hepatosplenomegaly Lymphadenopathy Bone pain (more common in children) |
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What tests would you order if you suspect acute leukaemia? |
FBC, Bone Marrow sample, Cytochemistry, Immunology, Cytogenetics, Molecular Genetics. |
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How do you distinguish between AML and ALL on the bone marrow analysis? |
In ALL cells in the Bone Marrow all look the same In AML Auer Rods are a characteristic feature |
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How do you manage a patient with Acute Leukaemia? |
Supportive care - antibiotics, platelets, blood transfusions Cytotoxic treatment - at least 2-3 cycles Hickman line CNS prophylaxis Stem Cell Transplant |
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When analysing the bone marrow, what indicates leukaemia? |
If the blast numbers are over 20% |
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How is remission defined? |
If the patient is clinically well, with a normal FBC, and the blast cells in the Bone Marrow are down to <5% |
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What is Acute Promyelocytic Leukaemia caused by? |
a very specific gene translocation |
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How do you manage a patient with Acute Promyelocytic Leukaemia? |
Give Supportive Care Treat with ATRA |
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A 17 year old woman comes in to ED due to car accident. Bleeding heaps, naturally, you wonder if she has Haemophilia. You test her FVIII and find it to be increased. Worried, you tell your consultant, and they look at you like you are an idiot. Why do they think you are an idiot? |
Because you are concerned by that! Factor VIII is an acute phase protein, so of course its gonna be raised! silly! |