Haematology Flashcards

Question

Explain the aetiology / risk factors of haemolytic anaemia.

Answer 1

Causes: - Autoantibodies - Medications - e.g. cephalosporins, dapsone, levodopa, levofloxacin, methyldopa, nitrofurantoin, NSAIDs, penicillins - Underlying malignancy - Hereditary conditions - e.g. hemoglobinopathies Risk factors: - Autoimmune disorders - Lymphoproliferative disorders - Prosthetic heart valve (mechanical, ball-and-cage devices, bileaflet valves) - Family origin in Mediterranean, Middle East, Africa or Southeast Asia - Family history of haemoglobinopathy or RBC membrane defects - Paroxysmal nocturnal haemoglobinuria - Recent exposure to cephalosporins, penicillins, quinine derivatives, or NSAIDs - Recent exposure to naphthalene or fava beans - Thermal injury - Exceptional exertion - Recent exposure to nitrites, dapsone, ribavirin, phenazopyridine - Recent paraquat ingestion - Malaria - Babesiosis - Bartonellosis - Clostridium perfringens infection - Haemophilus influenzae Type B infection - Liver disease

Answer 2

Hemolytic anemia represents approximately 5% of all anemias. Acute AIHA is relatively rare, with an incidence of one to three cases per 100,000 population per year. Hemolytic anemias are not specific to any race.

Answer 3

- Presence of risk factors - Fatigue - Shortness of breath - Dizziness - Dark urine - Active infections - e.g. malaria, Babesia, Bertonella, clostridial sepsis, pneumococci, E.coli, staphylococci - Triggered by exposure to cold

Answer 4

- Pallor - Jaundice - Splenomegaly - Dark urine

Answer 5

1st Line: - FBC - low Hb - MCHC - high (presence of spherocytes, reticulocytes) - Reticulocyte count - high rectiulocyte percentage (>1.5%), absolute reticulocyte count, recticulocyte index - Peripheral smear - schistocytes, spherocytes, elliptocytes, spur cells, blister cells, bite cells, tear drops, RBC inclusions (malaria, babesiosis, Bartonella infection) - Unconjugated (indirect) bilirubin - high! - LDH - high! - Haptoglobin - low! - binds free Hb with low plasma values = increased free Hb - Urinalysis - dipstick positive for blood, no RBCs = haemoglobinuria To consider: - Direct antiglobulin test (DAT or Coombs') - positive = immune aetiology, negative = non-immune aetiology - Creatinine, urea = thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome - LFTs - high in liver disease - Donath-Landsteiner antibody - cold-immune disease - Hb electrophoresis - HbS = sickle cell, HbA2 and HbF = beta-thalassaemia - Flow cytometry for CD55 / CD59 - abnormal (test for paroxysmal nocturnal haemoglobinuria clone - dark urine) - G6PD fluorescent spot test and spectrophotometry - low G6PD activity - ANA - positive if SLE (10% of cases)

Answer 6

Characterised by a triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI.

Answer 7

HUS - Shiga toxin-producing Escherichia coli (STEC) Atypical HUS - Abnormalities in the alternative complement regulatory pathway - Endothelial cell damage - Microvascular thombosis Risk factors: - Ingestion of contaminated food or water - Known community outbreak of Shiga toxin-producing E.coli - Exposure to infected individuals in institutional settings - Genetic predisposition to atypical HUS - Bone marrow transplant - Exposure to ciclosporin, chemotherapy, targeted cancer agents, quinine - Pregnancy or post-partum related

Answer 8

Ninety percent of HUS cases occur in the paediatric population, due to Shiga toxin-producing Escherichia coli(STEC) Atypical HUS can occur in adults, and in some children.

Answer 9

- Diarrhoea - Bloody diarrhoea - Childhood (< 5 years) Uncommon: - Known community outbreak of Shiga toxin-producing E-coli - History of ingestion of food that may have been contaminated with Shiga toxin-producing E-coli - Unusual side effect seen after treatment with ciclosporin, chemotherapy, quinine - Pregnancy or post-partum status - Unusual adverse effect seen after bone marrow transplant - Family history of possible HUS-like syndrome

Answer 10

- Diarrhoea - Bloody diarrhoea - Childhood (< 5 years) Uncommon: - Known community outbreak of Shiga toxin-producing E-coli - History of ingestion of food that may have been contaminated with Shiga toxin-producing E-coli - Unusual side effect seen after treatment with ciclosporin, chemotherapy, quinine - Pregnancy or post-partum status - Unusual adverse effect seen after bone marrow transplant - Family history of possible HUS-like syndrome

Answer 11

1st Line: - FBC - anaemia, thrombocytopenia - Peripheral blood smear - presence of schistocytes - Renal function / creatinine - increasing creatinine due to renal endothelial cell damage - Serum electrolytes - sodium, potassium, chloride, bicarbonate, calcium and phosphorus = high K+, low or high Na+, acidosis, high PO4, low HCO3 - PT/PTT - normal to rule out DIC - LDH - high (released from destroyed RBC) - Haptoglobin - low (binds free Hb released by destroyed RBC) - Stool culture on sorbitol-MacConkey agar - Shiga toxin-producing E.coli cannot ferment sorbitol, appears as white colonies - PCR - positive - Protein involved in complement regulation - abnormal levels of complement in familial and atypical HUS Consider: - Urinalysis - if renal involvement = haematuria, proteinuria or elevated creatinine level - ADAMTS13 level - normal in most cases - LFTs - transient transaminitis if hepatic involvement - Serum amylase, lipase, glucose - increased if pancreatic involvement

Answer 12

A bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor.

Answer 13

Haemophilia A - Deficiency of clotting factor VIII Haemophilia B - Deficiency of clotting factor IX Acquired haemophilia - Separate non-inherited condition - Much rarer than congenital haemophilia - Autoimmune-related aetiology - No genetic inheritance pattern Risk factors: - Family history of haemophilia (congenital) - Male sex (congenital) - Age > 60 years (acquired) - Autoimmune disorders - e.g. IBD, diabetes, hepatitis, pregnancy, postnatal, malignancy (acquired)

Answer 14

Hemophilia A is seen in about 1 in every 4,000–5,000 males worldwide, compared with hemophilia B, which is estimated to be in 1 in every 20,000 men. Hemophilia C, a much rarer form of the disease, is estimated to occur in about 1 case per 100,000 people in the U.S. Almost exclusively in males due to X-linked recessive pattern of inheritance.

Answer 15

- Presence of risk factors - History of recurrent or severe bleeding - Bleeding into muscles - Prolonged bleeding following heel prick or circumcision - Mucocutaneous bleeding - Haemarthrosis - Intracranial bleeding - Fatigue - Menorrhagia and bleeding following surgical procedures or childbirth (female carriers)

Answer 16

- Excessive bruising - Haematoma - Extensive cutaneous purpura (acquired) - GI bleeding (haematemesis or melena) - Haematuria - Distended and tender abdomen - Pallor - Tachycardia - Tachypnoea - Hypotension

Answer 17

1st Line: - aPTT - prolonged - Plasma Factor VIII and Factor IX assay - low (use to determine severity) - Mixing study - aPTT corrected by incubating patient plasma with normal plasma in congenital, not corrected if antibodies present in immune acquired - FBC - normal, low Hb if bleeding - PT - normal - Plasma vWF assay - normal - Plasma Factor V, VII, XI, XII assay - normal - Closure time/bleeding time and platelet aggregation studies - normal - Serum AST and ALT - normal (check for liver disease) - Plain XR of bony sites - demonstrate findings of acute joint bleeding (haemarthrosis) - Antenatal factor VIII or IX mutation analysis by amniocentesis or chorionic villus sampling (CVS) - specific genetic mutation identified Consider: - Head or neck CT - Head or neck MRI - Abdominal ultrasound or CT AP scan - OGD or colonoscopy - Blood factor VIII or IX mutation analysis - Plasma factor VIII or IX inhibitor screen - Bethesda assay / modified Bethesda assay on plasma sample - low-responder inhibitor

Answer 18

Primary = a haematological disorder characterised by isolated thrombocytopenia (platelet count <100 x 10^9/L) in absence of identifiable cause Secondary = all forms of ITP where associated medical conditions or precipitants can be identified. Distinction clinically relevant due to different natural histories and treatments, including need to treat the underlying condition in secondary ITP.

Answer 19

Primary = thrombocytopenia due to autoimmune destruction and involves antibody destruction of peripheral platelets. Risk factors: - Women of childbearing age - Age <10 or >65 years

Answer 20

Typically found in children often with a preceding viral illness and an abrupt onset. There is a female preponderance among adults, who may present with thrombocytopenia with or without bleeding. The prevalence (how many adults have ITP at any time) is 9.5 cases per 100,000. The annual prevalence is estimated at 5.3 per 100,000 among children; because children with ITP usually recover, the number of children who have ITP at any one time is almost equal to those diagnosed annually.

Answer 21

- Presence of risk factors - Bleeding - Absence of systemic symptoms - e.g. fever, weight loss, arthralgia, skin rash, skin rash, alopecia, venous thrombosis - Absence of medicines that cause thrombocytopenia - e.g. heparin, alcohol, quinine / quinidine, sulfa drugs - Absent splenomegaly or hepatomegaly - Absent lymphadenopathy

Answer 22

- Presence of risk factors - Bleeding - Absence of systemic symptoms - e.g. fever, weight loss, arthralgia, skin rash, skin rash, alopecia, venous thrombosis - Absence of medicines that cause thrombocytopenia - e.g. heparin, alcohol, quinine / quinidine, sulfa drugs - Absent splenomegaly or hepatomegaly - Absent lymphadenopathy

Answer 23

1st Line: - FBC - low platelets < 100 x 10^9/L - Peripheral blood smear - low platelets (distinguishes between true thrombocytopenia and pseudothrombocytopenia occuring when there is insufficient collection in 0.1% of adults) Consider: - HIV serology - H.pylori breath test or stool antigen test - Hepatitis C serology - TFTs - both hyper and hypothyroidism cause thrombocytopenia - Quantitative immunoglobulins - reveal common variable immunodeficiency or selective IgA deficiency - Bone marrow biopsy / aspiration - increased megakaryocytes, no malignancy or cytometry or cytogenetic abnormalities - Pregnancy test

Answer 24

A plasma cell dyscrasia characterized by terminally differentiated plasma cells, infiltration of bone marrow by plasma cells and the presence of monoclonal immunoglobulin (or immunoglobulin fragment) in serum and/or urine.

Answer 25

Risk factors: - Osteolytic bone disease - Anaemia - Renal failure - Abnormal free light-chain ratio - Monoclonal gammopathy of undetermined significance (MGUS) - Family history - Radiation exposure - Petroleum products exposure

Answer 26

Myeloma incidence rates are projected to rise by 11% in the UK between 2014 and 2035, to 12 cases per 100,000 people by 2035. [1] This includes a larger increase for males than for females. It is projected that 8,888 cases of myeloma (5,229 in males, 3,659 in females) will be diagnosed in the UK in 2035.

Answer 27

- Anaemia - Bone pain - Monoclonal gammopathy of undetermined significance (MGUS) - Infections - Fatigue - Renal impairment

Answer 28

- Anaemia - Bone pain - Monoclonal gammopathy of undetermined significance (MGUS) - Infections - Fatigue - Renal impairment

Answer 29

1st Line: - Serum / urine electrophoresis - paraprotein spike, hypogammaglobulinaemia (IgG >35g/L or IgA >20g/L and light chain urinary excretion >1g/day) - Skeletal survey - osteopenia, osteolytic lesions, pathological fractures - Whole-body, low-dose computed tomography (WBLD-CT) - osteolytic lesions (>5mm in diameter), pathological fractures - Serum-free light-chain assay - increased concentrations of free light chain in serum - Bone marrow aspirate and biopsy - monoclonal plasma cel infiltration in bone marrow >10% - Serum calcium - hypercalcaemia - FBC - anaemia - Creatinine, urea - renal impairment (creatinin >176 mmol/L) - Serum beta-2-microglobulin - correlates with clinical stages, <3.5mgd/dL (stage 1), >5.5mgL (Stage 3) - Serum albumin - prognostic significance - >35g/L (stage I) Consider: - Whole body MRI - >1 focal lesions on MRI study, bone marrow infiltration - 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) - bone disease, bone marrow infiltration - CRP - high or increasing - LDH - higher = more extensive disease - Cytogenetics & fluorescence in situ hybridisation analysis - chromosomal trisomies or monosomies

Answer 30

An uncommon haematological malignancy arising from mature B cells.

Answer 31

Characterized by the presence of Hodgkin's cells and Reed-Sternberg cells. Risk factors: - History of EBV infection - Family history - Young adults from higher socio-economic class - HLA types - Jewish ancestry

Answer 32

Hodgkin's lymphoma is a rare cancer of the lymphatic system that affects the B-lymphocytes and leaves a patient susceptible to infection. Estimates suggest that around 1 in 25,000 people are affected by this cancer every year and the condition accounts for just under 1% of all cancers that occur worldwide.

Answer 33

B-Symptoms: - Fevers - Night sweats - Weight loss Common presentation: - Painless - Cervical and/or supraclavicular lymphadenopathy - Young adult Uncommon factors: - Unexplained fevers - Night sweats - Weight loss - Dyspnoea - Cough - Chest pain - SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins - Abdominal pain - Generalised pruritus - Alcohol-induced pain at involved sites - Hepatomegaly and / or splenomegaly - Tonsillar enlargement

Answer 34

B-Symptoms: - Fevers - Night sweats - Weight loss Common presentation: - Painless - Cervical and/or supraclavicular lymphadenopathy - Young adult Uncommon factors: - Unexplained fevers - Night sweats - Weight loss - Dyspnoea - Cough - Chest pain - SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins - Abdominal pain - Generalised pruritus - Alcohol-induced pain at involved sites - Hepatomegaly and / or splenomegaly - Tonsillar enlargement

Answer 35

- FBC - low Hb and platelets, WBC may be high or low - Metabolic panel - normal - ESR - elevated - CXR - mediastinal mass, large mediastinal adenopathy (negative prognostic factor) - PET-CT scan - involved sites appear FDG-avid (bright) - Gallium scan - bright involved sites - Contrast CT neck, chest and AP - enlarged lymph nodes - Excisional lymph node biopsy - Hodgkin's cells - Immunohistochemical studies - CD30-positive, CD15-positive, CD45-negative, CD20 positive Investigations to consider: - Bone marrow biopsy - Hodgkin's cells - TFTs - abnormal in patients who receive radiotherapy to neck - Echo or multi-gated acquisition (MUGA) scan - Pulmonary function tests

Answer 36

A heterogeneous group of malignancies of the lymphoid system.

Answer 37

- Malignant lymphoid cells retain many qualities of their normal counterparts - e.g. defending organism from external and internal (neoplastic) threats - Boundaries between leukaemias and lymphomas are blurred - e.g. acute alymphocytic leukaemia and acute lymphoblastic lymphoma, chronic lymphocytic leukaemia and small lymphocytic lymphoma - Depends on relative presence of solid phase (lymphoma) versus circulating phase (leukaemia) Risk factors: - Age > 50 years - Male - Immunocompromised host - Epstein-Barr virus (EBV) - HTLV-1 virus - Herpes Virus-8 - H.pylori - Coeliac disease - HIV - Hepatitis C virus - Sjogren's syndrome - Wiskott-Aldrich Syndrome - Ataxia - Telangiectasia - Organ transplant - Borrelia burgdoferi - Rheumatoid arthritis - SLE - Common veriable immunodeficiency - Chediak-Higashi syndrome - Klinefelter's syndrome - Pesticides - Phenoxyherbicides - Breast implants

Answer 38

- 4% of total cancer cases - 80-84 years peak rate - Increase by 39% incidence rate since 1990s

Answer 39

- Night sweats - Weight loss - Fatigue / malaise - Fever - Shortness of breath - Cough - Abdominal discomfort - Headache - Change in mental status - Dizziness - Ataxia - Chest pain - Bone pain - Back pain - Jaundice - Pallor - Purpura - Skin lesions

Answer 40

- Fever - Lymphadenopathy - Splenomegaly - Hepatomegaly - Abdominal discomfort - Change in mental status - Jaundice - Pallor - Purpura - Skin lesions - Neuological abnormalities on examination

Answer 41

1st Line: - FBC - thrombocytopenia, pancytopenia, lymphocytosis from bone-marrow / liver involvement - Blood smear - nucleated red blood cells, left shift - Lymph node biopsy - positive - Skin biopsy - positive - Bone marrow biopsy - positive - Basic metabolic panel - normal or deranged kidney, electorlyte and glucose function - LFTs - elevated due to liver involvement - LDH - elevated Consider: - Flow cytometry - tumour surface markers determined, type of lymphoma - Immunohistochemistry - tumour surface markers determined, type of lymphoma - PCR for tumor markers - BCL1 and BLC2, TCR - Ig gene rearrangement studies - detection of rearrnaged genes - Cytogenetics studies with or without FISH - chromosomal translocations - Hep B and C serology - negative, if positive then risk of reatcivation, need to determine prior to chemo - HIV - positive or negative - LP - presence of abnormal cells, low glucose, high protein, high pressure (for Burkitt's lymphoma, primary CNS lymphoma, AIDS-related B-cell lymphoma, CNS relapse risk high) - Colonoscopy - micropolyps - CT - staging tool - Multiple-gated acquisition scan - cardiac baseline function - Echo - cardiac baseline function - PET scan - involved sites brightness

Answer 42

The clonal expansion of myeloid blasts in the bone marrow, peripheral blood or extramedullar tissue. Acute promyelocytic leukaemia (APML) - form of AML with normal WBC, bi-lobed nuclei, hypergranulated blasts, bundles of Auer rods.

Answer 43

A malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered through somatic changes and undergoes uncontrolled proliferation.

Answer 44

The malignant clonal disorder of haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow.

Answer 45

NB: The main difference between lymphocytic leukemias and lymphomas is that in leukemia, the cancer cells are mainly in the bone marrow and blood, while in lymphoma they tend to be in lymph nodes and other tissues. Chronic lymphocytic leukaemia: An indolent lymphoproliferative disorder in which monoclonal B lymphocytes are found in peripheral blood. (if found in lymph nodes = small lymphocytic lymphoma).

Answer 46

Leukaemia incidence rates are projected to rise by 5% in the UK between 2014 and 2035, to 19 cases per 100,000 people by 2035. [1] This includes an increase for males and a drop for females. It is projected that 13,758 cases of leukaemia (8,714 in males, 5,044 in females) will be diagnosed in the UK in 2035.

Answer 47

- Pallor - Ecchymoses or petechiae - Fatigue - Dizziness - Palpitations - Dyspnoea - Infections or fever - Lymphadenopathy - Hepatosplenomegaly - Mucosal bleeding

Answer 48

Dysregulation of haematopoiesis due to BCR-ABL fusion gene. Abnormal expansion of myeloid cells in bone marrow and peripheral blood. Chronic phase may transform to accelerated or blast phase in 5-10% of patients despite tyrosine kinase inhibitor treatment = acute myeloid or acute lymphoblastic leukaemia. Risk factors: - Age 65-74 years - Ionising radiation exposure - Male

Answer 49

Risk factors: - Age over 60 years - Male sex - White ethnicity - Family history of CLL

Answer 50

AML: - FBC - anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia - Peripheral blood smear - blasts on blood film, presence of Auer rods - Coagulation panel - if abnormal = DIC - Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid - Renal function - elevated urea - LFTs - normal or elevated - Serum lactic dehydrogenase - elevated - Bone marrow biopsy or aspiration - hypercellularity, infiltration - Immunophenotyping and molecular studies - specific lineage of blasts - Lumbar puncture- malignant cells - HLA antigen typing - CXR - consolidation, pulmonary infiltrates, cardiomegaly due to leukostasis - Echocardiogram - Multi-gated acquisition scan ALL: - FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia - Peripheral blood smear - leukaemic lymphoblasts - Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid - Renal function - elevated or normal urea - Liver function - elevated or normal - Lactic dehydrogenase - elevated - Coagulation profile - Bone marrow aspiration and trephine biopsy - hypercellularity, lymphoblastic infiltration - Immunophenotyping - TPMT phenotype - - Cytogenetics - Molecules studies - Philadelphia chromosome? - HLA-typing - CXR - mediastinal mass, pleural effusion, LRTI - LP - leukaemic lymphoblasts - Pleural tap - leukaemic lymphoblasts - CT / MRI brain - CT - Minimal residual disease molecular samples

Answer 51

- Presence of risk factors - Splenomegaly - Shortness of breath - Left upper quadrant discomfort or fullness - Epistaxis - Arthralgia - Sternal tenderness - Weight loss - Excessive sweating - Fever - Pallor - Bruising - Retinal haemorrhages

Answer 52

- Presence of risk factors - Splenomegaly - Shortness of breath - Left upper quadrant discomfort or fullness - Epistaxis - Arthralgia - Sternal tenderness - Weight loss - Excessive sweating - Fever - Pallor - Bruising - Retinal hemorrhages

Answer 53

- Shortness of breath and fatigue - Lymphadenopathy - Splenomegaly - Hepatomegaly - Presence of risk factors - B-symptoms - Recurrent infections - Petechiae

Answer 54

MCV >100 femtolitres [fL] Megaloblastic: a deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation. Non-megaloblastic: encompasses all other causes of macrocytic anaemia in which DNA synthesis is normal. Megaloblasts and hypersegmented neutrophils are absent.

Answer 55

MEGALOBLASTIC CAUSES: - VIT B12 DEFICIENCY - deficient intake, deficient IF (pernicious anaemia, gastrectomy), biological competition for B12 (diverticulosis, fistula, intestinal anastomosis, achlorhydria, infection by Diphylobothrium latum), selective B12 malabsorption (congenital and drug-induced), chronic pancreatitis, ileal resection - FOLATE DEFICIENCY - deficient intake, alcoholism, increased needs (pregnancy, infant, cirrhosis), malabsorption (congenital and drug-induced), intestinal and jejunal resection - TOXINS & DRUGS - amobarbital sodium, cycloserine, cytarabine, ethotoin, folic acid antagonist (methotrexate), pergolide, purine antagonist (6-mercaptopurine), pyrimidine antagonists (cytosine arabinoside), phenobarbital, pyrimethamine, secobarbital sodium, trimethoprim, erythroleukaemia NON-MEGALOBLASIC CAUSES: - Myelodysplasia - CLD - Reticulocytosis - Hypothyroidism Risk factors for MEGALOBLASTIC ANAEMIA: - Folate deficiency - Nutritional deficiency - e.g. strict vegan diet, malabsorption (bacterial overgrowth, sprue, Whipple's, Crohn's) , diphilobothrium lactum infection (competes for B12 absorption) - Elderly age - Alcohol use - Narcotic abuse - Pregnancy - Infancy - Low grade haemolysis - Malignancy - Chornic haemodialysis - Autoimmune disease - e.g. Hashimoto's, vitiligo, DM, adrenal insufficiency

Answer 56

Macrocytosis affects 2% to 4% of the population, 60% of whom have anemia

Answer 57

- Weight loss - Brittle nails - Tachycardia - Pallor - Confusion Myelodysplasia - Pallor - Petechiae - Purpura

Answer 58

- Appetite loss - Diarrhoea - Fatigue - Shortness of breath - Poor concentration Myelodysplasia - History of prior exposure to petroleum distillates, chemotherapy, radiotherapy - Fever - Chills - Fatigue - Weakness - Recurrent infection - Anorexia - NIght sweats - Shortness of breath - Easy bruising

Answer 59

VitB12 Deficiency - FBC with peripheral smear - megaloblastic macrocytic anaemia, basophilic stippling - Serum Vit B12 levels - low - Serum methylmalonic acid levels - high - Anti-IF antibodies- positive in pernicious anaemia - Anti-parietal cell antibodies - positive in pernicious anaemia Folate deficiency - FBC with peripheral smear - megaloblastic macrocytic anaemia, basophilic stippling - Serum folate - low - Serum Vit B12 levels - normal, low in combined deficiency - Serum homocysteine levels - high Toxins & Drugs Myelodysplasia - FBC - macrocytic anaemia with leukopenia, macro-ovalocytes, cytopenias (neutropenia, thrombocytopenia) - Reticulocyte count - <2% - Bone marrow aspiration and biopsy - myeloblasts with immature precursors - Cytogenetics of bone marrow biopsy - multiple chromosomal translocations possible (5q-, 7q- or trisomy 8) - Serum vitB12 - normal - Folate - normal CLD - FBC - non-megaloblastic macrocytic anaemia, thrombocytopenia - PT - decreased - LFTs - abnormal - Ab USS, CT, MRI - liver surface nodularity, small liver, possible hypertrophy of left /caudate lobe, evidence of ascites or collateral circulation - Liver biopsy - diagnosis of underlying cause or cirrhosis Hypothyroidism - FBC - non-megaloblastic macrocytic anaemia - Serum TSH - high - Serum T4 - reduced - Reticulocyte count - <2%

Answer 60

MCV <80 femtolitres [fL]

Answer 61

Children & Adolescents - Iron deficiency anaemia - Thalassemia trait - Othe hemoglobinopathies - Lead toxicity - Chronic inflammation - Sideroblastic anaemia Menstruating Women - Iron deficiency anaemia - Thalassaemia trait - Prgenancy - Anaemia of chronic disease - Sideroblastic anaemia Men and Non-Menstruating Women - Iron deficiency anaemia - Anaemia of chronic disease - Unexplained anaemia - Thalassaemia trait

Answer 62

According to epidemiologic data from World Health Organization (WHO), 24.8% of the human population is currently suffering from anemia out of which a major portion is due to iron deficiency anemia. Hypochromic microcytic anemia is more common in premenopausal females because they lose blood with each menstrual cycle. Among the female population, almost 41% of all pregnant females suffer from anemia while among nonpregnant pre-menopausal females 30% females are struggling with anemia. The male population is usually resistant to anemia due to circulating testosterone levels. However, 12.7% adult males are also globally afflicted with anemia. After the female population, pre-school aged children suffer the most from anemia because of lack of iron in their primary diet. Human milk contains 0.3 mg/L iron which does not provide enough iron. On the other hand, cow milk contains double the amount of iron, but that iron has poor bioavailability

Answer 63

History indicates: - Reduced dietary intake of iron - Increased blood loss in menstrual flow - Bleeding from git, particularly from gastric and duodenal ulcers - Malignancy or large gut - Major trauma after which iron stores become depleted Plummer-Vinson Syndrome - Complaining of food stuck inside chest - Due to oesophageal webs - Swollen tongue (glossitis) - Microcytic anemia ?PICA - Preference to eat non-nutritious substances - e.g. clay, ice, flour

Answer 64

- Pallor - hands, conjunctivita - Tachycardia - Increased RR - Exhaustion - Koilonychia - spoon-shaped nails - Signs and symptoms of angina due to decreased delivery of oxygen to cardiac myocytes

Answer 65

- FBC - low MCV, low MCHC - Iron studies - high TIBC, low transferrin saturation, ferritin <12ng/ml + no scurvey = iron deficiency - Pierpheral smear - small RBC, pencil cells, central pallor, peripheral rim of haemoglobin Low or normal ferritin level does not exclude diagnosis of iron deficiency anaemia as ferritin is an acute-phase reactant protein and levels increase during infection.

Answer 66

Treat underlying cause. IF HYPOCHROMIC MICROCYTIC ANAEMIA: After the diagnosis of hypochromic microcytic anemia is established, iron replacement therapy can be commenced. Therapy includes 325 mg of ferrous sulfate three times a day orally. Of this, up to 10 mg of iron can be absorbed from the gut and is the preferred initial treatment. Nausea and constipation are the side effects which limit the compliance of this therapy. Compliance can be increased by gradually increasing the dose of the treatment while monitoring the patient for side effects. The maximum tolerable dose is usually selected for the replacement of lost iron. The impact of this treatment usually appears after 3 weeks, while the full effects will be evident by 2 months. Parenteral iron products may be used when: - Oral drugs produce unrelenting side effects - The anemia is resistant to oral therapy - There is some git disease preventing proper absorption of iron - There is continued blood loss which cannot be corrected by oral supplementation. The iron preparation with sorbitol is slowly infused over 5 minutes at a dose of 50 mg/kg body weight in males and 35 mg/kg body weight in females. The parenteral dose is usually the iron deficit plus one extra gram of iron to replenish the iron reserves of the body.

Answer 67

- Fatigue - Weakness - Tiredness - Loss of stamina - Shortness of breath - Dizziness - Pale skin - Tissue hypoxia - Shock - Hypotension - Coronary or pulmonary insufficiency - Increased risk of infections - Motor or cognitive development delays in children - Pregnancy complications - e.g. preterm delivery, giving birth to baby with low birth weight

Answer 68

Depends on the cause and pathway through clinical treatment.

Answer 69

A group of clonal stem cell disorders, characterised by ineffective and dysplastic haematopoiesis resulting in 1 or more cytopenias, and a varying predilection to develop AML.

Answer 70

Can arise primarily without any inciting event or may be related to previous treatment with either chemotherapy or radiation. Risk factors: - Age >70 years - Alkylating agents - Topoisomerase inhibitors - Prior haematopoietic stem cell transplantation - DNA repair deficiency syndromes - Ionising radiation - Tobacco - Benzene - Aplastic anaemia - Paroxysmal nocturnal haemoglobinuria (PNH) - Down's Syndrome (trisomy 21) - Congenital neutropenia

Answer 71

The incidence of MDS increases markedly with age, and the disease is most prevalent in individuals who are white and male. It is conservatively estimated that >10,000 new cases of MDS occur in the United States annually, and that ≥60,000 individuals with MDS currently reside in the country.

Answer 72

- Older age - Asymptomatic - Fatigue - Exercise intolerance - Bacterial infection - Presence of risk factors - Autoimmune disorders

Answer 73

- Pallor - Petechiae - Purpura - Splenomegaly - Hepatomegaly - Lymphadenopathy

Answer 74

1st Line: - FBC with differential - one or more cytopenias - Reticulocyte count - normal or low - RBC folate - normal (rule out folate deficiency) - Serum B12 levels - normal - Iron studies - normal - HIV testing - negative - Bone marrow aspiration with iron stain - single or multilineage dysplasia, bone marrow blasts <20% - Bone marrow core biopsy - hypercellular marrow - Bone marrow cytogenetic analysis - chromosomal abnormalities e.g. deletion 5q31, monosomy 7, 11q23, deletion 17p, deletion 20q, abnormal 12p Investigations to consider: - Serum erythropoietin - high, or low in renal failure - HLA typing - varies - Flow cytometry - clonal population

Answer 75

A reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterized by the abnormal production of RBCs, WBCs and platelets, in association with marrow fibrosis (scarring) and extramedullary haematopoiesis.

Answer 76

Primary Myelofibrosis - Chronic progressive myeloproliferative disorder with origin in a multipotent haematopoietic progenitor cell - Aetiology unknown - Specific clonal marker not identified - Leukerythroblastosis + splenomegaly - Median survival 5.5 years but very heterogeneous - range from <1 year to >30 years Secondary or Reactive Myelofibrosis - When bone marrow fibrosis is due to a known diagnosis - E.g. leukaemia, hypoparathyroidism, drugs Risk factors: - Radiation exposure - Industrial solvents exposure - Age >65 years

Answer 77

The annual incidence of primary myelofibrosis (PMF) is approximately 1 case per 100,000 individuals, although an increased prevalence is noted in Ashkenazi Jews.

Answer 78

- Presence of risk factors - Weight loss - Night sweats - Low-grade fever - Cachexia - Fatigue - Pruritis -

Answer 79

- Splenomegaly - Hepatomegaly - Features of extramedullary hematopoiesis - Features of portal hypertension - Symptoms of pulmonary hypertension - Joint and bone pain - Hearing loss - Bleeding - Infections

Answer 80

1st Line: - FBC with differential - anaemia, normal or abnormal cell counts (leukocyte, platelet) - Peripheral blood smear - teardrop-shaped RBCs, metamyelocytes, myelocytes, promyelocytes, myeloblasts, nucleated RBCs in circulation - Bone marrow aspiration - unable to aspirate marrow - Bone marrow biopsy - marrow fibrosis (scarring) To consider: - Genetic mutation analysis - Breakpoint cluster region-abelson PCR - Chromosomal assessment in bone marrow examination - CD34+ cell count - Anti-nuclear antibodies - Rheumatoid factor titre - Complement levels - Coombs' test - Echo - USS of suspected site - Technetium-99 Scan - CT - MRI - Serum uric acid

Answer 81

Increased splenoportal blood flow and decreased hepatic vascular compliance. - Ascites - Oesophageal and gastric varices - GI bleeding - Hepatic encephalopathy - Hepatic or portal vein thrombosis

Answer 82

- Shortness of breath - Fatigue - Presyncope

Answer 83

MCV 80-100 femtolitres [fL]

Answer 84

HYPERPROLIFERATIVE - Reticulocyte count >2% - The proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction or loss of RBCs. - The cause is usually acute blood loss or haemolysis. HYPOPROLIFERATIVE - Reticulocyte count <2% - These are primarily disorders of decreased RBC production, and the proportion of circulating reticulocytes remains unchanged

Answer 85

Its prevalence increases with age, reaching 44 percent in men older than 85 years. Normocytic anemia is the most frequently encountered type of anemia. Anemia of chronic disease, the most common normocytic anemia, is found in 6 percent of adult patients hospitalized by family physicians.

Answer 86

- Fatigue - Pallor - Dizziness - Light-headedness - Shortness of breath

Answer 87

``` HYPOPROLIFERATIVE - exclude haematological malignancies, aplastic anaemia - Bleeding - Easy bruising - Night sweats - Weight loss ? Haematological malignancy ? Aplastic anaemia ``` - Symptoms and risk factors for infections that can cause self-limiting pure red cell aplasia - E.g. parvovirus infection, infectious mononucleosis, viral hepatitis, malaria, respiratory infections, gastroenteritis, mumps - Phenytoin, carbamazephine, sodium valproate, azathioprine, sulfonamides, isoniazide, procainamide = pure red cell aplasia - Benzene, penicillamine, gold= aplastic anaemia - Chloramphenicol = aplastic anaemia or pure red cell aplasia - Chemotherapy = pancytopenia - Autoimmune disease, chronic hepatitis = pure red cell aplasia - CKD or hypothryoidism symptoms HYPERPROLIFERATIVE - looking for haemorrhage & haemolytic anaemias - Drugs causing haemolysis - e.g. penicillin, methyldopa, levodopa, quinidines, cephalosporins, NSAIDs - Drugs causing haemolytic uraemic syndrome - e.g. cyclosporine, tacrolimus, clopidogrel, oral contraceptive pills, chemo drugs - Triggers of DIC - e.g. severe infection, sepsis, malignancy, obstetric emergency, trauma, burns, pancreatitis, liver failure, envenomation, drug overdose, endothelial damage - TTP - headache, confusion, focal weakness, seizures, coma, menorrhagia - Malignant hypertension - sudden-onset dizziness, headache, mental status changes, loss of sensation or motor strength, chest pain, pressure, dyspnoea, oedema - Prosthetic valve replacement - haemolysis induced by prosthesis - Bloody diarrhoea - suspicion of E.coli infection, haemolytic uraemic syndrome - SCA - pain in skeleton, chest, abdomen - Family history of sickle cell anaemia, hereditary spherocytosis, G6PD deficiency - History of autoimmune disease or lymphoproliferative disorders - can result in autoimmune haemolytic anaemia - Recent blood transfusion history - Occupational or home exposure - lead toxicity?

Answer 88

``` HYPOPROFILERATIVE - Ecchymoses - Petechiae ? Haematological malignancy ? Myelodysplastic syndrome ? Aplastic anaemia ``` - Lymphadenopathy - Fever ? Malignancy ? Infection - Splenomegaly ? Haematological malignancy HYPERPROLIFERATIVE - Purpura - Ecchymoses - Bleeding - Systolic BP >210 mmHg, Diastolic BP >130mmHg = malignant hypertension? - S3, new murmurs, JVP raised, oedema, oliguria, polyuria, focal neurological signs, hypertensive retinopathy = malignant hypertension? - Cutaneous reddish-brown or violaceous vascular lesions = haemangioma? - Splenomegaly = hereditary spherocytosis? - Autoimmune disease clinical features - Lymphadenopathy = ?infectious mononucleosis, ?leukaemia, ? lymphoma, ?autoimmune disease

Answer 89

HYPOPROLIFERATIVE - FBC - cytopenia (?haematological malignancy), pancytopenia (?aplastic anaemia, chemotherapy, radiotherapy), isolated anaemia (pure red cell aplasia, anaemia due to CKD) - Bone marrow biopsy - acute leukaemia, chronic myelogenous leukaemia, aplastic anaemia, bone marrow mets - Anti-parvovirus antibodies - positive in parvovirus infection (pure red cell aplasia) - Consider: hepatitis serology, monospot test, EBV antibodies, peripheral smear (malaria), TFTs, anti-nuclear antibodies (SLE, scleroderma), RF (RA), serum CK (dermatomyositis), erythropoietin levels (low in CRF), calcium & PTH (2ndary hyperparathyroidism), CXR (pneumonia, smooth mass in thymona) HYPERPROLFERATIVE - FBC - Peripheral smear - If suspect haemolytic anaemia, test serum LDH, haptoglobin, bilirubin Thrombocytopenia + schistocytes = microangiopathic haemolytic anaemia Spherocytes = autoimmune haemolytic anaemia, hereditary spherocytosis High MCH = hereidtary spherocytosis Sicked RBC = SCA Heinz bodies + eccentrocytes + bite cells = C6PD deficiency High LDH, high bilirubin, low haptoglobin = haemolytic anaemia Tests to consider in suspected microangiopathic haemolytic anaemias: - Serum creatinine, which may be elevated in patients with haemolytic uraemic syndrome or malignant hypertension. - Urine dipstick, which may show haematuria and/or proteinuria in haemolytic uraemic syndrome - Stool tests: culture, polymerase chain reaction for enterohaemorrhagic E. coli genes, or enzyme-linked immunosorbent assay for Shiga toxin in haemolytic uraemic syndrome.[67] - Prothrombin time and activated partial prothrombin time, which are prolonged in DIC but normal in other microangiopathic haemolytic anaemias. - DIC panel shows elevated D-dimers and fibrin degradation products with low fibrinogen in patients with DIC. - X-rays and magnetic resonance imaging (MRI) scanning of suspected regions reveal internal haemangiomas. Tests to consider in other haemolytic anaemias - Direct antiglobulin (Coombs') test, which is positive in autoimmune haemolytic anaemia. - Tests to identify hereditary causes. Sickle cell anaemia is diagnosed on FBC. Osmotic fragility test is positive in hereditary spherocytosis; cells lyse on exposure to hypo-osmotic solution. G6PD assays identify deficiencies of the enzyme. - Tests to identify infection. Monospot test or viral capsid antigen IgM is positive in infectious mononucleosis. CMV IgM is positive in CMV infection. Double-sandwich IgM enzyme-linked immunosorbent assay (ELISA) or IgG avidity test is positive for IgM in acute toxoplasmosis. Splenic or bone marrow aspirate shows amastigotes of the parasite in leishmaniasis. - Blood lead levels, which are elevated in lead toxicity.

Answer 90

POLYCYTHAEMIA / ERYTHROCYTOSIS - An abnormally high Haematocrit and Hb concentration ABSOLUTE ERYTHROCYTOSIS - Increase in total number of red blood cells in circulation - Increased red cell mass - Classified as primary, secondary and idiopathic PRIMARY ERYTHROCYTOSIS - Caused by polycythaemia vera SECONDARY ERYTHROCYTOSIS - Caused by increased production of erythropoietin - Due to chronic tissue hypoxia caused by chronic lung disease - Due to kidney disorders, renal tumours and hepatomas APPARENT ERYTHROCYTOSIS - Increased Haematocrit and Hb concentration with NORMAL red-cell mass - Caused by low plasma volume most commonly occurs in people taking thiazides, heavy smokers or heavy alcohol users POLYCYTHAEMIA VERA - A clonal haematopoietic disorder characterised clinically by erythrocytosis, thrombocytosis, leukocytosis and splenomegaly. - Increased risk of thrombosis and haemorrhage. - Belongs to the group of Philadelphia chromosome-NEGATIVE myeloproliferative neoplasms - NB: JAK2 V617F mutation

Answer 91

POLYCYTHAEMIA / ERYTHROCYTOSIS - An abnormally high Haematocrit and Hb concentration ABSOLUTE ERYTHROCYTOSIS - Increase in total number of red blood cells in circulation - Increased red cell mass - Classified as primary, secondary and idiopathic PRIMARY ERYTHROCYTOSIS - Caused by polycythaemia vera SECONDARY ERYTHROCYTOSIS - Caused by increased production of erythropoietin - Due to chronic tissue hypoxia caused by chronic lung disease - Due to kidney disorders, renal tumours and hepatomas - Risk factors - cardiac and respiratory symptoms or disease, smoking, potential exposure to carbon monoxide, excessive daytime sleepiness, snoring, sleep disturbances, previous renal transplantation APPARENT ERYTHROCYTOSIS - Increased Haematocrit and Hb concentration with NORMAL red-cell mass - Caused by low plasma volume most commonly occurs in people taking thiazides, heavy smokers or heavy alcohol users - Risk factors - obesity, smoking, alcohol excess, hypertension, thiazide diuretics, testosterone, anabolic steroids POLYCYTHAEMIA VERA - A clonal haematopoietic disorder characterised clinically by erythrocytosis, thrombocytosis, leukocytosis and splenomegaly. - Increased risk of thrombosis and haemorrhage. - Belongs to the group of Philadelphia chromosome-NEGATIVE myeloproliferative neoplasms. - Risk factors: Age > 40 years, Budd-Chiari Syndrome, affected family member

Answer 92

The prevalence of polycythaemia vera has been estimated to be approximately 22 cases per 100,000 population[4]. It is believed to occur more frequently among Jews of Eastern European descent than other Europeans and Asians.

Answer 93

Hyperviscosity Symptoms: - Chest and abdominal pain - Myalgia and weakness - Fatigue - Headache - Tinnitus - Blurred vision, temporary loss of vision in one or both eyes - Paresthesia - Slow mentation, sense of depersonalisation - Bruising - Pruritis - contact with warm water - Abdominal discomfort - relating to splenomegaly - Hyperhidrosis - Tenderness or painful burning and/or redness of fingers, plams, heels or toes

Answer 94

- Ruddy complexion - Conjunctival plethora - Splenomegaly (polycythaemia vera) - Abdominal masses - e.g. benign and malignant uterine, renal and hepatic tumours which may be palpable and secreting erythropoietin - Oxygen saturation <92% in room air - Clubbing of digits - Abnormal heart or breath sounds

Answer 95

- Urine dipstick - identify renal causes of secondary erythrocytosis - Hb - MCV - Haematocrit - WCC - Platelets - LFTs - U&E - eGFR Erythrocytosis = Hb > 185g/L, Haematocrit > 0.52 (M) 0.48 (F). Polycythaemia vera = high WCC, high platelet, high Haematocrit, low MCV, normal LFTs Budd-Chiari Syndrome = high LFts Abnormal LFTs - ?secondary erythrocytosis, ?hepatic tumour Abnormal renal function - ?secondary erythrocytosis, ?renal cause ADDITIONAL INVESTIGATIONS - Serum erythropoietin — high = secondary erythrocytosis, low = polycythaemia vera - Serum ferritin — low MCV = iron deficiency? - JAK2 V617F mutation — positive = polycythaemia vera - Serum uric acid — high = polycythaemia vera. - Abdominal ultrasound -splenomegaly = polycythaemia vera

Answer 96

Caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in the production of sickle cell haemoglobin (HBS). Other forms may occur if HbS is inherited from one parent and another abnormal haemoglobin, or beta thalassaemia, is inherited from the other parent - e.g.HbSC or HbSB thalassaemia. Sickle cell trait occurs if HbS is inherited from one parent and normal HbA from the other.

Answer 97

Risk factors: - Genetic - autosomal recessive pattern When both parents carry the recessive sickle gene, there is a 1 in 4 chance that their offspring will inherit two recessive alleles, causing sickle cell anaemia.

Answer 98

SCD affects approximately 100,000 Americans. SCD occurs among about 1 out of every 365 Black or African-American births. SCD occurs among about 1 out of every 16,300 Hispanic-American births. About 1 in 13 Black or African-American babies is born with sickle cell trait (SCT)

Answer 99

- Parent diagnosed with sickle cell anaemia, other sickle cell diseases, or sickle cell trait - Persistent pain in skeleton, chest and/or abdomen - Dactylitis - Bone pain - Visual floaters - Lethargy

Answer 100

- High temperature - Pneumonia-like syndrome - Tachypnoea - Failure to thrive - Pallor - Jaundice - Tachycardia - Maxillary hypertrophy with an overbite - Protuberant abdomen, often with an umbilical hernia - Cardiac systolic flow murmur - Shock

Answer 101

1st Line: - DNA based assays - replacement of both beta haemoglobin subunits with HbS, 1 normal and 1HbS is sickle cell trait - Haemoglobin isoelectric focusing (Hb IEF) - Cellulose acetate electrophoresis - 75-95% HbS, absent HbA for sickle cell anaemia - High-performance liquid chromatography (HPLC) - Haemoglobin solubility testing - >10-15% HbS - Peripheral blood smear - presence of nucleated red blood cells, sickle-shaped cells, Howell-Jolly bodies - FBC and reticulocyte count - degree of anaemia occurs in most patients - Iron studies - normal or elevated serum iron, transferrin, ferritin levels, serum iron-binding capacity Consider: - Pulse oximetry - oxygen desaturations in acute chest syndrome - Plain XR of long bones - infarctions seen by irregular margins or moth-eaten destruction with overlying periosteal new bone formation - Bacterial cultures - bacterial pathogen culture may confirm infection - CXR - pulmonary infiltrates (acute chest syndrome)

Answer 102

Vaso-Occlusive Crisis - Analgesia - Supportive care + correction of cause - e.g. cold exposure, acidosis - Antihistamines - diphenhydramine - Hydration - Antibiotics - Blood transfusion Acute Chest Syndrome - Oxygen and incentive spirometry (prevent atelectasis) - Analgesia - Broad-spectrum antibiotics - Antihistamines - diphenhydramine - Blood transfusion - Hydration Chronic Disease SCA - Supportive care + prevention of complications - Hydroxycarbamide - L-glutamine - Crizanlizumab - Voxelotor - repeated blood transfusions - Bone marrow transplantation Variant SCD - Supportive care + prevention of complications - Hydroxycarbamide - Crizanlizumab - Repeated blood transfusions - Bone marrow transplantation

Answer 103

- Painful crises - obstruction of small blood capillaries - Anaemia (varying degrees) - Red cell haemolysis - Damage to major organs - Increased vulnerability to severe injections - Stroke - Acute chest syndrome - Vaso-occlusive crisis

Answer 104

Although people with sickle cell anemia tend to have a shorter life expectancy than is seen in the general population, advances in treatments — such as the approval of hydroxyurea and Endari (L-glutamine) — have improved survival and patients’ quality of life. Potential new therapies are also being developed.

Answer 105

Folate - found in green vegetables, nuts, yeast and liver Synthesised by the gut bacteria Body stores last for 4 months Maternal folate deficiency causes foetal neural tube defects. Is absorbed by duodenum and proximal jejunum.

Answer 106

Causes: - Poor diet - e.g. poverty, alcoholics, elderly - Increased demand - e.g. pregnancy, high cell turnover - seen in haemolysis, malignacy, inflammatory disease, renal dialysis - Malabsorption - e.g. coeliac disease, tropical sprue - Alcohol - Drugs - anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim Risk factors: - Low dietary folate intake - Age >65 - Alcoholism - Pregnant or lactating

Answer 107

Lower income economies - >20% | Higher income economies - <5%

Answer 108

- Presence of risk factors - Prolonged diarrhoea - Headache - Loss of appetite - Weight loss - Fatigue

Answer 109

- Presence of risk factors - Prolonged diarrhoea - Headache - Loss of appetite - Weight loss - Fatigue

Answer 110

- Bloods - peripheral blood smear, FBC, reticulocyte count, serum folate, red blood cell folate, vitB12, LDH

Answer 111

A clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura.

Answer 112

Absence of von Willebrand factor cleaving enzyme (ADAMTS-13) - 33% of idiopathic patients. Results in unusually large von Willebrand multimers. Leads to platelet aggregation and thrombocytopenia & microthrombi. Risk factors: - Black ethnicity - Female gender - Obesity - Pregnancy - Cancer therapies - HIV infection - Bone marrow transplantation - Anti-platelet agents - Quinine

Answer 113

TTP is a rare disease; the exact prevalence is not clear. Studies cite incidences between 1 and 13 cases per million people depending on geographic location. TTP most often occurs after 40 years of age, but congenital forms can occur in children.

Answer 114

PENTAD: - Fever - Renal failure - Haemolytic anaemia - Thrombocytopenia - Neurological changes Signs & Symptoms: - Non-specific prodrome - Severe neurological symptoms - e.g. coma, focal abnormalities, seizures - Mild neurological symptoms - e.g. headache, confusion - Age 30-50 - Digestive symptoms - e.g. N&V, diarrhoea, abdominal pain - Weakness - Bleeding symptoms - purpura, ecchymosis, menorrhagia

Answer 115

PENTAD: - Fever - Renal failure - Haemolytic anaemia - Thrombocytopenia - Neurological changes Signs & Symptoms: - Non-specific prodrome - Severe neurological symptoms - e.g. coma, focal abnormalities, seizures - Mild neurological symptoms - e.g. headache, confusion - Age 30-50 - Digestive symptoms - e.g. N&V, diarrhoea, abdominal pain - Weakness - Bleeding symptoms - purpura, ecchymosis, menorrhagia

Answer 116

1st Line: - Platelet count - LOW - Haemoglobin - < 8g/L - Haptoglobin - LOW - Peripheral smear - microangiopathic blood film with schistocytes - Reticulocyte count - HIGH - Urinalysis - proteinuria - Urea and Creatinine - HIGH - Direct Coombs' test - NEGATIVE (rule out autoimmune haemolytic anaemia) Consider: - ADAMTS-13 activity assay and inhibitor titres - decreased activity

Answer 117

Beta-Thalassaemia - An inherited microcytic anaemia caused by the mutation of the beta-globin gene leading to decreased or absent synthesis of beta-globin, resulting in ineffective erythropoiesis Alpha Thalassaemia - A group of disorders of haemoglobin synthesis, caused by mutations or deletions in at least 1 of the 4 alpha-globin genes, leading to variably impaired alpha-globin chain production - Accumulation of the now excess and unpaired beta-globin chains

Answer 118

Beta-Thalassaemia The genotypic spectrum includes homozygous and heterozygous defects, which result in a phenotypic spectrum ranging from transfusion dependence to the asymptomatic carrier state. Compound heterozygosity of beta-thalassaemia with haemoglobin E mutations results in a phenotype more severe than either beta-thalassaemia trait or haemoglobin E mutations alone, similar to beta-thalassaemia major or intermedia. Risk factors: - Positive family history Alpha Thalassaemia There are at least 4 different and distinct alpha-thalassaemias: silent carrier (1 affected alpha-globin gene), alpha-thalassaemia trait (2 affected alpha-globin genes), Hb H disease (typically 3 affected alpha-globin genes), and Hb Bart hydrops fetalis syndrome (typically deletion of all 4 alpha-globin genes). Risk factors: - Ethnicity from a geographic malarial area - Positive family history

Answer 119

BETA The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Beta-thalassemia is prevalent in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The highest carrier frequency is reported in Cyprus (14%), Sardinia (10.3%), and Southeast Asia. The high gene frequency of beta-thalassemia in these regions is most likely related to the selective pressure from Plasmodium falciparum malaria. ALPHA The incidence of HbH disease in these countries is approximately 4-20 individuals per every 1,000 births. Some studies have estimated that as much as 5% of the world's population carries an alpha-thalassemia variant (i.e., a mutation in one of the two pairs of genes associated with alpha thalassemia). Alpha-thalassaemia is found in malarial regions of the world (Mediterranean, South-east Asia, Indian sub-continent, Middle East, Sub-Saharan Africa) and should be suspected in patients with these ethnic backgrounds and with microcytosis and/or anaemia.

Answer 120

BETA - Country of origin or ancestry - Family history - Asymptomatic - Lethargy - Abdominal distension - Failure to gain weight - Low height and weight - Pallor - Spinal changes - Large head - Chipmunk facies - Misaligned teeth - Hepatosplenomegaly - Jaundice ALPHA - Presence of risk factors - Family history of alpha-thalassaemia - Symptoms of anaemia - Splenomegaly - Childhood or young adulthood - Symptoms of gallstones - Growth retardation - History of prior iron supplementation - Jaundice - Mild dysmorphic facial features - Extramedullary haematopoiesis

Answer 121

BETA - Country of origin or ancestry - Family history - Asymptomatic - Lethargy - Abdominal distension - Failure to gain weight - Low height and weight - Pallor - Spinal changes - Large head - Chipmunk facies - Misaligned teeth - Hepatosplenomegaly - Jaundice ALPHA - Presence of risk factors - Family history of alpha-thalassaemia - Symptoms of anaemia - Splenomegaly - Childhood or young adulthood - Symptoms of gallstones - Growth retardation - History of prior iron supplementation - Jaundice - Mild dysmorphic facial features - Extramedullar haematopoiesis

Answer 122

BETA - FBC - microcytic anaemia, Normal /HIGH WCC, Normal /HIGH platelets - Peripheral smear - microcytic red cells, tear drops, microspherocytes, target cells, some fragments, large number of nucleated red cells - Reticulocyte count - HIGH - Haemoglobin analysis - major (no HbA, high HbF, high HbA2), intermedia (low HbA, high HbF, high HbA2), trait (HbA, high HbF, high HbA2) - LFTs - elevated total and unconjugated bilirubin, high LDH - Plain X Rays of Skull - widening of the diploeic space, facial deformity - Abdominal ultrasonography - liver and spleen enlargement - Plain X-Rays of long bones - widening of diploeic space, osteopenia - Genetic testing - HLA typing - degree of match between patient and siblings ALPHA 1st Line: - Hb - normal to low - MCV - LOW - MCH - LOW - RBC - HIGH - Peripheral smear - abnormal shape and size of cells - Reticulocyte percentage - HIGH - Serum iron - normal to HIGH - Serum ferritin - normal to HIGH Investigations to Consider: - Brilliant cresyl blue staining of red blood cells - Hb H inclusions in peripheral blood red cells - Haemoglobin electrophoresis - presence of HbH, HbBart and concomitant haemoglobinpathies - Hb fractionation by high-performance liquid chromatography (HPLC) - presence of HbH, HbBart and concomitant haemoglobinpathies - Gap-PCR - detect specific deletions - Multiplex ligation-dependent probe amplification (MLPA) - detect deletion alleles - Direct sequencing - detect non-deletional alpha-thalassaemia mutations - MRI (hepatic or cardiac) - hepatic or cardiac iron in patients with iron overload demonstrated by difference in organ-to-muscle signal intensity - Superconducting quantum interference devices (SQUID) - hepatic iron in iron overload - Liver biopsy - liver iron >5mg/gram dry weight on liver biopsy = need for iron chelation therapy

Answer 123

The most common inherited bleeding disorder.

Answer 124

Due to either a quantitative or qualitative abnormality of VWF. VWF provides the critical link between platelets and exposed vascular subendothelium, and also binds and stabilises coagulation factor VIII. Most patients have Type 1, more severe are in Type 2 and 3. Autosomal inheritance with variable penetrance and phenotypic expression. Risk factors: - Positive family history - Consanguineous relationships - Lymphoproliferative disorders - Aortic stenosis - Myeloproliferative disorders - Hypothyroidism

Answer 125

Prevalence. Von Willebrand disease (VWD) occurs with equal frequency among men and women, affecting up to 1% of the general population. However, women are more likely to experience symptoms of VWD because of the increased bleeding it causes during their menstrual periods, during pregnancy, and after childbirth.

Answer 126

- Presence of risk factors - Bleeding from minor wounds - Post-operative bleeding - Family history of bleeding - Easy and excessive bruising - Menorrhagia - GI bleeding - Epistaxis - Blood transfusions - Haemarthrosis - CNS bleeding - Haematuria

Answer 127

- Presence of risk factors - Bleeding from minor wounds - Post-operative bleeding - Family history of bleeding - Easy and excessive bruising - Menorrhagia - GI bleeding - Epistaxis - Blood transfusions - Haemarthrosis - CNS bleeding - Haematuria

Answer 128

1st Line - PT - within the reference range - APTT - prolonged if Factor VIII activity is < 35% of normal - FBC - normal (except in Type 2B which may show a low platelet count) - VWF antigen - diagnostic if < 0.30 IU/mL - VWF function assay - ristocetin cofactor and collagen binding assays - diagnostic if VWD < 0.30 iu/mL, ratio of function to antigen <0.6 diagnoses Type 2 VWD - Factor VIII activity - frequently higher than vWF antigen level in Type 1, Type 2 factor VIII < vWF antigen activity level To consider: - VWF multimer analysis - type 1: all multimers present, decreased in intensity; type 2A, loss of medium- and high-molecular-weight multimers; type 2B, loss of high-molecular-weight multimers; type 2M, normal multimers - Platelet aggregometry - aggregation to low conc of ristocetin (< 0.7mg/ml) = Type 2B VWD - Factor VIII - VWF binding assay - decreased binding in Type 2N - TFTs - acquired VWD in hypothyroidism - Serum protein electrophoresis - monoclonal gammopathy consistencies Emerging Tests - Mutation analysis- mutations consistent with diagnosis of VWD - PFA-100 and other platelet function analysers - specific abnormla results

Answer 129

COMMON - Trauma - normal/low Hct, low Hb, reactive leukocytosis, reactive thrombocytosis, thrombocytopenia (dilution of transfusion), normal PT/APTT - Acute GI bleeding - normal/low Hct, low Hb, reactive leukocytosis, reactive thrombocytosis, >2% reticulocyte count, normal PT/APTT, high PT/APTT in cirrhosis etc, high urea - Rupture of vascular aneurysm - normal/low Hct, low Hb, reactive leukocytosis, reactive thrombocytosis, >2% reticulocyte count - Surgery - normal/low Hct, low Hb, reactive leukocytosis, reactive thrombocytosis - Menorrhagia - microcytic anaemia, normal WBC, reactive thrombocytosis (if iron def), normal PT/APTT - Iron deficiency - microcytic anaemia, thrombocytosis, low serum iron, high TIBC, low ferritin, high solule transferrin receptor - Vitamin B12 def - megaloblastic macrocytic anaemia, basophilic stippling, low B12, high methylmalonic acid, high anti-IF / pariteal cell antibodies in pernicious anaemia - Folate B12 def - megaloblastic macrocytic anaemia, basophilic stippling, low folate, normal B12, high homocysteine levels - Myelodysplastic syndrome - macrocytic anaemia, leukopenia, macro-ovalocytes, neutropenia, thrombocytopenia, <2% reticulocyte count, myeloblasts, immature precursors, chromosomal translocations - ALL - pancytopenia, >20% blasts, normocytic anaemia, hypereosinophilia, <2% reticulocyte count - AML - pancytopenia, >20% blasts, normocytic anaemia, hypereosinophilia, <2% reticulocyte count - CML - normocytic anaemia, myeloid maturing cells, high basophils, high eosinophils, <2% reticulocyte count, hypercellular with granulocytic hyperplasia (bone marrow), Philadelphia chromosome (BCR-ABL translocation t(19;22)), high uric acid - Hairy cell leukaemia - pancytopenia, normocytic anaemia, <2% reticulocyte count, hairy cells on bone marrow - Acquired aplastic anemia - pancytopenia, macrocytosis, normocytic anaemia, <2% reticulocyte count, hypocellular bone marrow (decrease in all elements), replaced by fat cells, no infiltration by fibrosis or malignant cells - Infiltration by secondary malignancy - pancytopenia, teardrop cells, poikilocytes, normocytic anaemia, <2%, infiltration of marrow space by malignant cells - Pure red cell aplasia - normocytic anaemia, <2% - Drug toxicity - normocytic anaemia, inhibitors of DNA synthesis/folate/B12 produces megaloblastic macrocytic anaemia, <2% if suppress bone marrow, >2% if drugs produce haemolysis, high bilirubin (haemolysis) - Anaemia of chronic disease - normocytic anaemia, low/normal iron, low TIBC, normal/high ferritin, high erythropoietin (low in CKD) - CKD - normocytic or microcytic anaemia, thrombocytosis, <2%, high creatnine, haematuria, proteinuria, low iron, high ferritin, high TIBC (iron def), normal or low erythropoietin level, low calcium and high PTH (hyperPTH secondary) - CLD - non-megaloblastic macrocytic anaemia, thrombocytopenia, low PT, abnormal LFTs - Pregnancy - microcytic anaemia with thrombocytosis (iron def), megaloblastic macrocytic anaemia (folate def) UNCOMMON - Generalised malnutrition - microcytic anaemia (iron def), megaloblastic macrocytic anaemia (vitB12, folate def), normocytic anaemia (vit & min def) - Cytotoxic chemotherapy - pancytopenia with normocytic anaemia, <2% - Radiotherapy - anaemia (pancytopenia) - Alcohol abuse - macrocytic anaemia - Lead toxicity - normocytic anaemia, basophilic stippling, >2%, high blood lead level - Hypothyroidism - non-megaloblastic macrocytic anaemia, high TSH, low T4, <2% - Autoimmune haemolytic anaemia (AIHA) - normocytic anaemia, spherocytes, >2% (4%), high LDH, low haptoglobin, positive Coombs', high bilirubin - Transfusion reaction - Malaria - normocytic anaemia, thrombocytopenia, leukopenia, >2% (4%), intracellular parasites with Wright's or Giemsa staining, high bilirubin - Viral hepatitis - normocytic anaemia, <2%, high ALT/AST - Toxoplasmosis - normocytic anaemia, thrombocytopenia, leukocytosis, eosinophilia, >2% (4%), IgM in acute infection, IgG chronic infection or previous infection - Leishmaniasis - normocytic anaemia, thrombocytopenia, leukopenia, erythroblastosis, positive for Leishmania antibodies, >2%, - Parvovirus B19 infection - normocytic anaemia, <2%, positive anti-parvovirus B19 antibodies - Infectious mononucleosis - normocytic anaemia, spherocytes, atypical lymphocytes, >2% (4% if haemolytic), <2% if pure red cell aplasia, high LDH, low haptoglobin - Cytomegalovirus (CMV) - normocytic anaemia, >2%, high LDH, low haptoglobin - Sickle cell anaemia - normocytic anaemia, sickle cells, 2%, high HbS/A ratio, high LDH, high bilirubin - Thalassaemias - microcytic anaemia with MCV close to 70, low MCHb, target cells, high HbF, high ferritin in overload - Hereditary spherocytosis - normocytic anaemia, high MCHb, spherocytes, >2%, positive osmotic fragility test - Glucose-6-phosphate dehydrogenase deficiency (G6PD) - normocytic anaemia, Heinz bodies, eccentrocytes, bite cells, >2%, low haptoglobin, high LDH, high bilirubin - Bone marrow failure syndromes - pancytopenia with normocytic or macrocytic anaemia, <2% - Haemolytic uraemic syndrome - normocytic anaemia, thrombocytopenia, schistocytes, >2%, normal PT/APTT, low haptoglobin, high LDH, high creatinine, high bilirubin - Disseminated intravascular coagulation (DIC) - normocytic anaemia, thrombocytopenia, schistocytes, high PT, varied APTT, high d-dimer & fibrin degradation products, low fibrinogen - Thrombotic thrombocytopenic purpura - normocytic anaemia, schistocytes, >2% - Haemangioma - normocytic anaemia, thrombocytopenia, >2%, soft-tissue shadows in XR, phleboliths - Malignant hypertension - normocytic anaemia with schistocytes, >2%, ischaemia or infarct on ECG, high creatinine (renal failure) - Prosthetic valves and surfaces - normocytic anaemia with schistocytes, >2% - Cutaneous burns - normocytic anaemia with thrombocytopenia, schistocytes from peripheral destruction on blood smear,>2%

Haematology Flashcards

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