Haematology Flashcards

Question

What is the prognosis of microcytic anaemia?

Answer 1

Depends on the cause

Answer 2

A type of anaemia which results in panyctopenia with hypocellular bone marrow without any abnormal cells, usually due to autoimmune destruction of haematopoeitic stem cells.

Answer 3

Most often IDIOPATHIC (> 40%): May be due to destruction or suppression of stem cells via autoimmune mechanisms Acquired: Drugs (e.g. chloramphenicol, sulphonamides, methotrexate) Chemicals (e.g. benzene, DDT, insecticides) Radiation Viral infection (e.g. parvovirus B19, EBV, HIV) Paroxysmal nocturnal haemoglobinuria (PNH) ``` Inherited: Fanconi’s anaemia - pancytopenia, short stature, microcephaly, developmental delay, cafe-au-lait spots, predisposition to malignancy, absent or hypoplastic thumbs Dyskeratosis congenita (rare, progression bone marrow failure syndrome) ```

Answer 4

Equal between males and females (perhaps slightly more common for males) Biphasic distribution - 10-25 years and >60 years old peak Fanconi anaemia is one of the most common congenital causes

Answer 5

``` Can be slow or rapid onset: Fatigue Pallor Dyspnoea Recurrent infections Mucosal bleeding Easy bruising Bleeding gums Epistaxis ```

Answer 6

Anaemia signs: pallor Thrombocytopenia signs: bruises, petechiae NO HEPATOSPLENOMEGALY OR LYMPHADENOPATHY

Answer 7

FBC - low Hb - normocytic anaemia, thrombocytopenia, leukopenia Serum erythropoeitin - elevated Reticulocyte count - decreased Bone marrow biopsy - hypocellular (low haematopoeitic stem cells), no abnormal cells, dry tap Fanconi’s Anaemia: Check for the presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents.

Answer 8

An acquired syndrome characterised by widespread activation of coagulation pathways, resulting in the formation of intravascular thrombi. This can lead to organ ischaemia, necrosis and failure, but also uses up clotting factors and platelets which can lead to spontaneous bleeding. Acute overt form where there is bleeding and depletion of platelets and clotting factors Chronic non-overt form where thromboembolism is accompanied by generalised activation of the coagulation system

Answer 9

Sepsis Malignancy Obsteteric complications - Missed miscarriage, severe pre-eclampsia, amniotic emboli, Placental abruption Trauma Intravascular haemolysis Immunological reactions - blood transfusion reactions, organ transplant rejection Severe organ destruction or failure (severe pancreatitis, acute hepatic failure) Vascular disorders (Kasabach-Merritt syndrome or giant haemangiomas, large aortic aneurysms) Severe toxic reactions

Answer 10

Seen in severely ill patients

Answer 11

Patients severely unwell with symptoms of underlying disease Oligouria - suggests circulatory collapse Dsypnoea Cough Confusion/delirium Evidence of Bleeding - epistaxis, gingivial bleeding

Answer 12

Signs of underlying disease Fever Evidence of shock - hypotension, tachycardia Acute DIC: Petechiae, purpura, ecchymoses Bleeding: Epistaxis, Mucosal bleeding, Overt haemorrhage, haematuria Signs of end organ damage – local infarction or gangrene Oliguria due to renal failure Respiratory distress Delirium and coma Chronic DIC: Signs of deep vein and arterial thrombosis or embolism Superficial venous thrombosis

Answer 13

``` Serum platelets - low Serum fibrinogen - low D-dimer - high Fibrin degradation products - elevated Prolonged PT Prolonged PTT Hb - decreased ``` Peripheral Blood Film: Schistocytes (red blood cell fragments)

Answer 14

A progressive myeloproliferative disorder in which the bone marrow gets replaced by fibrosis and extramedullary haematopoiesis occurs, resulting in splenomegaly. It is also associated with pancytopenia.

Answer 15

Primary myelofibrosis: due to mutation in haematopoietic stem cells - often JAK2 mutation Primary stem cell defect is UNKNOWN - results in increased numbers of abnormal megakaryocytes which release growth factors resulting in fibrosis Seconary myelofibrosis: caused by essential thrombocthaemia or polycythaemia vera - 30% of patients have a history of one of these

Answer 16

``` Occurs in adults More common in White patients More common in males Median age at diagnosis is 65 years old RARE Peak onset = 50-70 ```

Answer 17

Can be asymptomatic and diagnosed after routine blood count ``` Bone pain History of frequent infections Fatigue Easy bruising Fever Itching Weight loss Anorexia Night sweats ``` ``` UNCOMMON: LUQ pain Indigestion (due to massive splenomegaly) Bleeding Gout ``` Symptoms of pulmonary hypertension due to extramedullary haematopoeisis in lungs: Shortness of breath Fatigue Presyncope

Answer 18

Hepatosplenomegaly | Petechiae

Answer 19

FBC - anaemia, thrombocytopenia, leukocytopenia LFTs - abnormal Peripheral blood film - tear drop RBCs, increased number of abnormal megakaryocytes, pancytopenia, immature nucleated RBCs, red and white cell precursors in film Bone marrow aspiration - dry tap Bone marrow biopsy - trephine biopsy shows fibrotic hypercellular marrow

Answer 20

Characterised by ineffected and dysplastic haematopoeisis, leading to abnormal cell maturation and cytopenias, with <20% bone marrow being made up of blasts.

Answer 21

Primary myelodysplasia is most common and is idiopathic Secondary myelodysplasia can be due to chemotherapy or radiotherapy, DNA alkylating agent use May have chromosomal abnormalities ``` Risk factors: Age > 70 years Alkylating Agents Topoisomerase Inhibitors Prior Haematopoietic Stem Cell Transplantation DNA Repair Deficiency Syndrome ```

Answer 22

Median age 65-70 years old Secondary can occur in younger patients More common in males

Answer 23

Can be asymptomatic and diagnosed on routine bloods ``` Symptoms of pancytopenia: Anaemia: Fatigue Dizziness Decreased exercise tolerance ``` Leukopenia: Increased recurrent infections Thrombocytopenia: Easy bruising Epistaxis Occupational exposure to toxic chemicals Prior chemotherapy or radiotherapy

Answer 24

Anaemia: Pallor, cardiac flow murmur Thrombocytopenia: Petechiae, purpura, ecchymosis Leukopenia: infections Gum hypertrophy

Answer 25

FBC - anaemia, thrombocytopenia, leukopenia Bone marrow aspirate - increased blast cells in bone marrow (<20%), dysplastic cells Bone marrow biopsy - hypercellularity Peripheral blood smear: ringed sideroblasts, large oval shaped RBCs, abnormal WBCs and platelets

Answer 26

A bleeding disorder caused by a quantitative deficiency or functional defiency of von Willebrand factor, resulting in mucocutaneous bleeding, increased bleeding after trauma, easy bruising and menorrhagia. Type I - decreased quantity of vWF Type II - decreased function of vWF, but normal levels Type III - severe quantitative deficiency/NO vWF

Answer 27

Mutation in vWF gene Type I - decreased amounts of vWF, AUTOSOMAL DOMINANT, most common Type II - normal quantities but abnormal function, AUTOSOMAL DOMINANT Type III - no vWF - AUTOSOMAL RECESSIVE Rarely can get acquired von Willebrand's disease: Lymphoproliferative disorders - multiple myeloma Aortic stenosis Myeloproliferative disorders Hypothyroidism vWF is an adhesive bridge between platelets and the exposed subendothelial collagen vWF also binds to factor VIII stabilising it and thus preventing its degradation

Answer 28

``` Family history of Von Willebrand Disease Consanguineous relationships Lymphoproliferative disorders Aortic Stenosis Myeloproliferative disorders Hypothyroidism ```

Answer 29

It is the most common inherited bleeding disorder Males and females affected equally Most common form is type 1 - 75% of cases Women more often diagnosed due to more severe symptoms - menorrhagia Type 2 and type 3 have more severe symptoms

Answer 30

Mucocutaneous bleeding - gingival bleeding Menorrhagia Easy bleeding from trauma Easy and excessive bruising Epistaxis - prolonged or requires medical intervention Excessive/prolonged bleeding from minor wounds or gums after dental procedures GI Bleeding CNS bleeding Haematuria

Answer 31

Petechiae Ecchymoses Hemarthrosis

Answer 32

Platelets - normal PT - normal PTT - increased due to decreased factor VIII activity Bleeding time - increased vWF function assay ristocetin assay - usually would cause platelet aggregation Factor VIII activity decreased vWF antigen – DIAGNOSTIC if <0.3 international units/mL

Answer 33

A bleeding disorder characterised by a lack of or lack of effectiveness of clotting factors which is usually inherited via an X-linked recessive pattern, but can be aqcuired. Haemophilia A is most common - deficiency of factor VIII Haemophilia B - deficiency of factor IX Haemophilia C - deficiency of factor XI

Answer 34

Due to deficiency in one or more clotting factors Inherited haemophilia due to X-linked recessive inheritance Haemophilia A is mutation in F8 gene on X chromosome - causes factor VIII deficiency Haemophilia B is mutation in F9 gene on X chromosome - causes factor IX deficiency ``` Acquired haemophilia: Renal failure DIC Autoimmune attack of clotting factor Vitamin K deficiency ``` ``` Risk factors of acquired haemophilia: Age > 60 IBD Diabetes Hepatitis Pregnancy Postpartum Malignancy ```

Answer 35

Mostly seen in males Men have disease, women are carriers Haemophilia A is more common

Answer 36

``` Prolonged bleeding following injury Easy bruising Severe nosebleeds Oozing following dental procedures Haematuria Blood in stool HAEMARTHROSIS - Painful swelling of joints without trauma/occuring spontaneously Painful bleeding into muscles Bleeding usually deep eg into muscles and joints ``` Female carriers usually asymptomatic - may have excessive bleeding after trauma

Answer 37

``` Haemarthrosis: Painful joint Swelling Decreased range of movement Warmth ``` Muscle haematomas/painful bleeding into muscles: Pain, swelling, decreased range of motion, erythema, increased local warmth Ecchymosis Excessive bruising Extensive Cutaneous Purpura Nerve palsies (due to nerve compression by haematomas) ``` Signs of Iron Deficiency anaemia: Pallor Fatigue Weakness SOB ```

Answer 38

FBC- normal platelets, may be anaemic due to bleeding Bleeding time - normal PT - normal PTT - prolonged Genetic testing Mixing study - aPTT normal Coagulation factor assays - decreased factor 8, 9 or 11

Answer 39

Immune destruction of platelets due to IgG autoantibodies resulting in bruising and bleeding tendency. Primary ITP - isolated thrombocytopenia with no underlying cause Secondary ITP - due to underlying systemic cause, often virus eg HIV, HCV, CMV or SLE

Answer 40

Mostly idiopathic Autoantibodies against platelet GlpIIb/IIIa receptor causing autoimmune destruction of platelets Secondary has underlying cause: Viruses - HCV, HIV, CMV, malaria - often causes ACUTE ITP following viral infection in children Autoimmune conditions - SLE, thyroid disease Malignancy Drugs (e.g. quinine)

Answer 41

Acute ITP - children post-infection Childhood ITP equal between sexes and has spontaenous resolution within 2 months Chronic - females of child bearing age

Answer 42

``` Asymptomatic Easy bruising Purpura Petechiae on lower limbs Submucosal bleeding Epistaxis Menorrhagia ```

Answer 43

Visible petechiae Bruises Haemorrhagic bullae No hepatosplenomegaly No lymphadenopathy No systemic symptoms

Answer 44

DIAGNOSIS OF EXCLUSION FBC - isolated thrombocytopenia PT, PTT, fibrinogen - NORMAL Autoantibodies - antiplatelet antibodies present Peripheral blood smear - isolated thrombocytopenia HIV and Hepatitis serology - look for secondary cause Bone Marrow Biopsy/aspiration – to exclude other pathology: normal or increased megakaryocytes

Answer 45

A disorder causing extensive microscopic clots to form in the small blood vessels throughout the body. A condition characterised by a pentad of symptoms: Microangiopathic haemolytic anaemia Thrombocytopenic purpura Neurological deficits Fever Renal failure

Answer 46

Deficiency in ADAMTS13 likely due to autoimmune antibody destruction ADAMRS13 usually cleaves vWF Abnormally large vWF multimers form which causes large clots to develop ``` Risk factors: Female SLE African Sepsis Pregnancy Liver disease Pancreatitis ```

Answer 47

RARE More common in women More common in black patients Average age 39 years old

Answer 48

Neurological - headache, seizure, coma, confusion Microangiopathic haemolytic anaemia - dark urine, fatigue, weakness Fever Easy bruising Mucocutaneous bleeding - menorrhagia, epistaxis GI symptoms - diarrhoea, nausea, vomiting, abdo pain Renal failure - oligouria/anuria, haematuria

Answer 49

``` Pallor (due to anaemia) Jaundice (due to haemolysis) Bruising (severe thrombocytopenia) Generalised oedema Hypertension Retinopathy ``` Gastrointestinal: Abdominal tenderness CNS: Weakness, reduced vision, fits, reduced consciousness

Answer 50

FBC - thrombocytopenia, normocytic anaemia, increased reticulocytes Creatinine and urea - elevated due to renal failure Increased potassium, decreased sodium LDH increased Unconjugated bilirubin - elevated Peripheral blood smear - schistocytes, thrombocytopenia, increased reticulocytes, spherocytes Urinalysis - haematuria, proteinuria ADAMTS13 activity assay - decreased

Answer 51

An autoimmune disease caused by the presence of antiphospholipid autoantibodies, resulting in thrombocytopenia, arterial and venous thrombosis and pregnancy-related morbidity.

Answer 52

Aetiology unknown Antiphospholipid antibodies such as anti-beta2-glycoprotein-1, anticardiolipin and lupus anticoagulant cause the formation of thromboses Risk factors: History of SLE or autoimmune rheumatological disorders Other autoimmune diseases Autoimmune haematological disorders

Answer 53

Can be primary or secondary Secondary often associated with SLE More common in young women

Answer 54

``` Symptoms of DVT - painful, swollen leg Headache, seizures Symptoms of MI, stroke, limb ischaemia History of miscarriages History of pregnancy loss or pregnancy related morbidity History of vascular thrombosis ```

Answer 55

New onset murmur - development of Libman-Sacks endocarditis Livedo reticularis - mottled blue/purple rash Features of thrombocytopenia - petechial rash, mucosal bleeding Arthralgia/arthritis Signs of SLE: Malar Flush, Discoid Lesions, Photosensitivity Oedema

Answer 56

FBC - decreased platelets Clotting Screen - increased APTT U&Es - increased creatine and urea due to antiphospholipid nephropathy ELISA Testing for: Anticardiolipin and Anti-β2-glycoprotein 1 antibodies Lupus Anti-coagulant Assays: Clotting assays showing effects of APL on the phospholipid dependent factors in coagulation cascade

Answer 57

A chronic condition caused by inheritance of HbS, leading to sickling of haemoglobin which results in anaemia, painful crises and red blood cell haemolysis.

Answer 58

It is an autosomal recessive disorder Mutation of the 6th amino acid from glutamic acid to valine on the beta globin chain Causes sickling of RBCs when deoxygenated Sickled cells are prone to premature destruction and occlusion of small blood vessels, causing painful crises and end organ damage ``` Sickling precipitated by: Acidosis Dehydration Hypoxia Infection ```

Answer 59

Common in Africa and south Asia where plasmodium falciparum malaria is common Symptoms present a few months after birth when HbA overtakes HbF as the predominant haemoglobin

Answer 60

Symptoms due to anaemia: Fatigue SOB Symptoms due to vaso-occlusion: Hands and feet - dactylitis - swollen painful fingers and toes Painful crises MAINLY affect the ribs, spine, pelvis & long bones in ADULTS Pulmonary vessels - acute chest syndrome - chest pain, SOB, cough Penis - priapism - painful prolonged erection Renal papillae - haematuria Auto splenectomy: increased risk of infections with encapsulated organisms (e.g. pneumococcus, meningococcus) Abdominal Pain (may get bilirubin gallstones) Myalgia and Arthralgia CNS - Fits and strokes (hemiplegia) Retina - Visual loss (proliferative retinopathy)

Answer 61

Signs of haemolytic anaemia: Pallor Scleral icterus Jaundice Enlarged cheeks Hepatomegaly due to extramedullary haematopoeisis Bone: joint or muscle tenderness or swelling (due to avascular necrosis) Retina: Cotton wool spots (retinal ischaemia) Signs secondary to sequestration crisis: Tachycardia Splenomegaly (later reduces in size due to splenic atrophy) Priapism

Answer 62

FBC - anaemia, increased reticulocytes LFTs - increased LDH and unconjugated bilirubin Decreased haptoglobin Protein electrophoresis - HbS dark band as opposed to normal HbA Peripheral blood smear - Howell-Jolly bodies and target cells (suggest hyposplenism), sickled cells, reticulocytes, anisocytosis (variation in size) Sickle Solubility Tests: Dithionate added to blood causes increased turbidity in sickle cell disease Hip X-Ray: Femoral head is a common site of avascular necrosis MRI or CT Head: If there are neurological complications

Answer 63

``` Advice: Avoid triggers - excessive exercise, excessive hot or cold, high altitude, dehydration Good hygiene and nutrition Genetic counselling Prenatal screening ``` Painful occlusive crisis: Oxygen and IV fluids - remove triggers IV opioids analgesia Antibiotics Prophylaxis due to autosplenectomy: Penicillin V, regular vaccinations (against capsulated bacteria) Folic Acid: If severe haemolysis or in pregnancy HYDROXYUREA: Increases HbF, reduces the frequency and duration of sickle cell crisis Red Cell Transfusion - For SEVERE anaemia and repeated crises Need to give with iron chelation to prevent iron overload Surgical: Bone marrow transplantation Joint replacement in cases with avascular necrosis

Answer 64

``` Increased susceptibility to infection with encapsulated-bacteria Acute chest syndrome Priapism Painful occlusive crises Anaemia Bilirubin gallstones Splenic sequestration Pulmonary hypertension Aplastic crises: infection with Parvovirus B19 - temporary cessation of erythropoiesis Haemolytic crises Cholecystitis Renal papillary necrosis Leg ulcers Cardiomyopathy ```

Answer 65

Most patients who manage it well will survive until around the age of 50 years Mortality is usually the result of pulmonary or neurological complications in ADULTS and infection in CHILDREN Most common cause of death is upper respiratory tract infection

Answer 66

Anaemia due to the premature destruction of erythrocytes, leading to decreased RBC lifespan less than 120 days.

Answer 67

Hereditary: Membrane Defects: Hereditary Spherocytosis, Elliptocytosis Metabolic Defects: G6PD deficiency, Pyruvate kinase deficiency Haemoglobinopathies: Sickle cell disease, Thalassemia Acquired: Autoimmune: Antibodies attach to erythrocytes - intravascular/extravascular haemolysis Iso-immune: transfusion reaction, haemolytic disease of the Newborn Drugs: Penicillin, Quinine (formation of a drug-antibody-erythrocyte complex) Trauma: Microangiopathic haemolytic anaemia (caused by RBC fragmentation in abnormal microcirculation) - haemolytic Uraemic syndrome, DIC, malignant hypertension Infection: Malaria, Sepsis Paroxysmal Nocturnal Haemoglobinuria ``` Risk factors: Autoimmune disorders Lymphoproliferative Disorders Prosthetic Heart Valve Family history of haemoglobinopathy or RBC Membrane Defects Paroxysmal Nocturnal Haemoglobinuria ```

Answer 68

COMMON Genetic causes are prevalent in African, Mediterranean & Middle Eastern populations Hereditary spherocytosis: most common inherited haemolytic anaemia in Northern Europe

Answer 69

``` Fatigue Pallor Shortness of breath Dizziness Jaundice Haematuria Dark urine ```

Answer 70

Jaundice Pallor Hepatosplenomegaly

Answer 71

FBC: Decreased Hb Increased reticulocytes, increased MCV, increased unconjugated BR Decreased haptoglobin (a protein that binds to free Hb released by RBCs) U&Es: Increased creatinine and urea in Thrombotic Thrombocytopenic Purpura or Haemolytic Uraemic Syndrome Peripheral Blood Films: Leucoerythroblastic, macrocytosis, nucleated erythrocytes or reticulocytes, polychromasia, specific abnormal cells such as: Spherocytes, Elliptocytes, Sickle Cell, Schistocytes, Malaria Parasites Urine: Increased urobilinogen Haemoglobinuria, Hemosiderinuria Direct Coombs’ Tests: Tests for autoimmune haemolytic anaemia, identifies erythrocytes coated with antibodies Osmotic fragility test or Spectrin mutation analysis: Identifies membrane abnormalities Ham's Test: Lysis of erythrocytes in acidified serum in Paroxysmal Nocturnal Haemoglobinuria Hb Electrophoresis or Enzyme Assays: To exclude other causes Bone Marrow Biopsy (rarely performed): Erythroid Hyperplasia

Answer 72

A triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney failure. Most commonly diarrhoea-associated and caused by enterohaemorrhagic e.coli, causing a prodrome of bloody diarrhoea and abdominal pain. Associated with TPP which also has fever and neurological symptoms more than the abdominal and kidney features.

Answer 73

``` Diarrhoea associated: Enterohaemorrhagic E. coli Shigella Camplyobacter Salmonella ``` Atypical haemolytic uraemic syndrome: Genetic mutations Medication - COCP, Ciclosporin, Mitomycin, 5-Flurouracil Autoimmune Other causes: malignant hypertension, malignancy, pregnancy, SLE, scleroderma

Answer 74

Uncommon Diarrhoea-positive HUS caused by shiga-toxin producing e. coli most common in CHILDREN TTP mainly affects adult females

Answer 75

Symptoms of e. coli infection: Bloody diarrhoea Abdominal pain ``` Symptoms of MAHA: Pallor Fatigue Jaundice Weakness Lethargy ``` Symptoms of thrombocytopenia: Easy bruising Purpura Symptoms of acute kidney failure: Oligo/anuria Haematuria TTP: Fever CNS changes - visual disturbance, altered mental status

Answer 76

``` Fever Hepatosplenomegaly Pallor Jaundice Purpura Abdominal tenderness Periorbital oedema Peripheral oedema ``` CNS (especially in TTP): Weakness, reduced vision, fits, reduced consciousness

Answer 77

FBC - thrombocytopenia, normocytic anaemia, increased neutrophils LDH - raised ESR/CRP - raised Unconjugated bilirubin - elevated U+Es - increased urea, creatinine and K+, decrease Na+ PT and PTT - normal Peripheral blood smear - schistocytes, helmet cells Urinalysis - haematuria, proteinuria, increased urea and creatinine Stool culture