Haematology Flashcards

Question

What are the clinical features of delayed transfusion reaction?

Answer 1

usually minimal but can include unexplained pyrexia, jaundice or unexplained drop in hemoglobin

Answer 2

Urinalysis shows urobilinogenuria and a blood shows fragile ballooned spherocytes, diagnosis is confirmed by Coombs test which is done by adding antihuman globulin (AHG) (anti-Ig G and anticomplement) to the patient’s washed RBCs. A positive test results in red cell agglutination.

Answer 3

Cold AIHA is usually by IgM and causes hemolysis best at 4°C. Hemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Reynaud’s and acrocynaosis. Patients respond less well to steroids. Causes of cold AIHA • Neoplasia: e.g. lymphoma • Infections: e.g. mycoplasma, EBV

Answer 4

Warm AIHA the antibody (usually IgG) causes hemolysis best at body temperature and hemolysis tends to occur in extravascular sites, for example the spleen. Management options include steroids, immunosuppression and splenectomy. Causes of warm AIHA • Autoimmune disease: e.g. Systemic lupus erythematosus* • Neoplasia: e.g. Lymphoma, CLL • Drugs: e.g. Methyldopa

Answer 5

Hereditary spherocytosis

Answer 6

Autosomal Dominant defect of RBC cytoskeleton • Biconcave disc → spherocyte • Red cell survival ↓, destroyed by spleen

Answer 7

Presentation • E.g. Failure to thrive • Jaundice, gallstones • Splenomegaly • Aplastic crisis precipitated by parvovirus infection • Degree of hemolysis variable • ↓ MCV - ↑ MCHC - ↑ Reticulocytes Splenic rupture is an important differential

Answer 8

the osmotic fragility test was previously the recommend investigation of choice. However, it is now deemed unreliable and is no longer recommended the British Journal of Haematology (BJH) guidelines state that 'patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration[MCHC], increase in reticulocytes) do not require any additional tests if the diagnosis is equivocal the BJH recommend the cryohaemolysis test and EMA binding for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Answer 9

Folate replacement • Splenectomy

Answer 10

Autosomal Recessive. It s caused by mutation in β-globin chain of hemoglobin, causing hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the 6th position. The β-globin gene is found on the short arm of chromosome 11.

Answer 11

Sickle-cell anemia is a specific form of sickle-cell disease in which there is homozygosity for the mutation, it is also known as "HbSS", "SS disease", "hemoglobin S". • Heterozygous: 1 sickle gene and 1 normal gene, it is known as "HbAS" or "sickle cell trait". • Other, rarer forms of sickle-cell disease include sickle-hemoglobin C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia (HbS/β0). These other forms of sickle-cell disease are compound heterozygous states in which the person has only one copy of the mutation that causes HbS and one copy of another abnormal hemoglobin allele.

Answer 12

Thrombotic, 'painful crises' • Aplastic • Sequestration (spleen, liver and kidney) • Hemolytic

Answer 13

Also known as painful crises or vaso-occlusive crises • Precipitated by infection, dehydration, deoxygenation • Infarcts occur in various organs including the bones (e.g. avascular necrosis of hip), hand-foot syndrome in children, lungs, spleen and brain.

Answer 14

Caused by infection with parvovirus • Sudden fall in hemoglobin

Answer 15

Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia • Acute chest syndrome: dyspnea, chest pain, pulmonary infiltrates, low PO2 - the most common cause of death in adults (Hydroxyurea ↓ the incidence of acute chest syndrome) • The most common cause of death in childhood: infraction and infection (Pneumococcus, Chlamydia, Mycoplasm)

Answer 16

Rare • Fall in hemoglobin due an increased rate of hemolysis

Answer 17

Anti gastric parietal cell antibodies in 90% (but low specificity) • Anti intrinsic factor antibodies in 50% (specific for pernicious anemia)

Answer 18

Macrocytic anemia • Low WBC and platelets

Answer 19

Also low serum B12, hypersegmented polymorphs on film, megaloblasts in marrow

Answer 20

Radiolabelled B12 given on two occasions • First on its own • Second with oral Intrinsic Factor • Urine B12 levels measured used in the past

Answer 21

condition where red cells fail to completely form heme, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired

Answer 22

Delta-aminolevulinate synthase-2 deficiency

Answer 23

Myelodysplasia • Alcohol • Lead • Chloramphenicol and Anti-TB medications (INH + Pyrazinamide)

Answer 24

Hypochromic microcytic anemia (more so in congenital) • Bone marrow: sideroblasts and ↑ iron stores

Answer 25

Supportive • Treat any underlying cause • Pyridoxine may help

Answer 26

is diagnosed when there is unexplained anaemia and reticulocytopenia, with a complete absence of red cell precursors in the bone marrow, but with preservation of other cell lines.

Answer 27

Either spontaneously or associated with • Thymoma • Autoimmune • Lymphoproliferative disorders.

Answer 28

is supportive with immunosuppression with cyclosporin or related compounds. The condition can rarely occur where recombinant erythropoietin is administered, where antierythropoietin antibodies can be detected; these patients respond to withdrawal of erythropoietin with subsequent falling of the antibody levels

Answer 29

is the commonest red cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans

Answer 30

Neonatal jaundice is often seen • Intravascular hemolysis • Heinz bodies on blood films

Answer 31

Diagnosis is made by using a G6PD enzyme assay

Answer 32

Anti-malarials: primaquine • Ciprofloxacin • Sulfonamides • Co-trimoxazole (because it contains sulfa)

Answer 33

Penicillins • Cephalosporins • Macrolides (Azithro-Clarithro-Erythro mycins) • Tetracyclines • Trimethoprim

Answer 34

is an acquired disorder leading to hemolysis (mainly intravascular) of hematological cells. It is thought to be caused by ↑ sensitivity of cell membranes to complement due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis

Answer 35

GPI can be thought of as an anchor which attaches surface proteins to the cell membrane • Complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI • Thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation

Answer 36

Hemolytic anemia • Red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopenia may be present • Hemoglobinuria: classically dark-colored urine in the morning (although has been shown to occur throughout the day) • Thrombosis e.g. Budd-Chiari syndrome • Aplastic anemia may develop in some patients

Answer 37

Flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham's test as the gold standard investigation in PNH • Ham's test: acid-induced hemolysis (normal red cells would not)

Answer 38

• Blood product replacement • Anticoagulation • Eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular hemolysis • Stem cell transplantation

Answer 39

analgesia e.g. opiates rehydrate oxygen consider antibiotics if evidence of infection blood transfusion exchange transfusion: e.g. if neurological complications

Answer 40

hydroxyurea increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years

Answer 41

Dehydration • Stress: Gaisbock syndrome

Answer 42

Polycythaemia Rubra Vera

Answer 43

COPD • Altitude • Obstructive sleep apnoea • Excessive erythropoietin: cerebellar hemangioma, hypernephroma, hepatoma, uterine fibroids*

Answer 44

Erythroid colony studies: autonomous growth of erythroid colonies is taken as a sign of primary polycythaemia, where erythropoiesis has escaped the control of erythropoietin; erythroid colony studies are thought to have high specificity for detecting primary versus secondary polycythaemia.

Answer 45

To differentiate between true (primary or secondary) polycythaemia and relative polycythaemia red cell mass studies are sometimes used. In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg

Answer 46

is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to ↑ RBCs, often accompanied by ↑ WBC (neutrophils) and ↑ platelets.

Answer 47

The incidence of PRV peaks in the sixth decade (50-60s of age)

Answer 48

Hyperviscosity (headaches, tinnitus, visual disturbance, cyanosis, joint pain) • Pruritus, typically after a hot bath • Splenomegaly ± Hepatomegaly • Hemorrhage (secondary to abnormal platelet function not number) • Plethoric appearance • Low ESR • Hypertension in a third of patients

Answer 49

a mutation in JAK2 is present in approximately 95% of patients

Answer 50

FBC/film (raised hematocrit; neutrophils, basophils, platelets raised in half of patients) • JAK2 mutation • Serum ferritin • Renal and liver function tests ↑ Hemoglobin and hematocrit • ↑ Leucocyte alkaline phosphatase (LAP) and low ESR • Additional: o ± ↑ WBC and ↑ PLT o ± ↑ Plasma volume o ↑ Vitamin B12 o ↑ Red cell mass o ↓ Erythropoietin level

Answer 51

Red cell mass • Arterial oxygen saturation • Abdominal ultrasound • Serum erythropoietin level • Bone marrow aspirate and trephine • Cytogenetic analysis • Erythroid burst-forming unit (BFU-E) culture

Answer 52

• Venesection - first line treatment • Hydroxyurea -slight ↑ risk of secondary leukemia • Allopurinol & Phosphorus-32 therapy

Answer 53

Diagnosis: JAK2-positive PRV - diagnosis requires both criteria to be present A1 High hematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted) A2 Mutation in JAK2 JAK2-negative PRV - diagnosis requires A1 + A2 + A3 + either another A or two B criteria A1 Raised red cell mass (>25% above predicted) OR hematocrit >0.60 in men, >0.56 in women A2 Absence of mutation in JAK2 A3 No cause of secondary erythrocytosis A4 Palpable splenomegaly A5 Presence of an acquired genetic abnormality (excluding BCR-ABL) in the hematopoietic cells B1 Thrombocytosis (platelet count >450 * 109/l) B2 Neutrophil leucocytosis (neutrophil count > 10 *109/l in non-smokers; > 12.5*109/l in smokers) B3 Radiological evidence of splenomegaly B4 Endogenous erythroid colonies or low serum erythropoietin

Answer 54

on a routine full blood count (CBC) is one of the most common enquiries received by hematologists from primary care physicians and hospital doctors. Neutropenia is defined as an absolute peripheral blood neutrophil count of <2.0 × 10*9/l. There is a racial variation: black and Middle Eastern people may have neutrophil counts of <1.5 × 10*9/l normally.

Answer 55

• Kostmann’s syndrome • Chediak–Higashi • Schwachmann–Diamond syndrome • Cyclical neutropenia

Answer 56

• Infection: viral e.g. influenza, HIV, hepatitis, bacterial sepsis. • Drugs: anticonvulsants (phenytoin) – anti-thyroid (carbimazole) – phenothiazines (chlorpromazine) – antibacterial agents (cotrimoxazole) – ACE-inhibitors (ramipril) • Immune-mediated: SLE, Felty’s syndrome (Rheumatoid Arthritis + Neutropenia + Splenomegaly) • Bone marrow failure: leukaemia, lymphoma, Hematinic deficiency • Splenomegaly: any cause

Answer 57

• Blood film • Hematinics: factors that ↑Hb (Iron, TIBC, Vit B12, Folic Acid, Vit D) • Autoimmune profile bone marrow aspirate/trephine are indicated if there are severe or prolonged neutropenia or features suggestive of marrow failure

Answer 58

describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. This may be due to infiltration of the bone marrow causing the immature cells to be 'pushed out' or sudden demand for new cells

Answer 59

• Severe infection • Severe hemolysis • Massive hemorrhage • Metastatic cancer with bone marrow infiltration

Answer 60

Leukemoid reaction: • High leukocyte alkaline phosphatase score • Toxic granulation (Dohle bodies) in the white cells • 'Left shift' of neutrophils i.e. ↑neutrophils or ≤ 3 segments of the nucleus CML: • Philadelphia chromosome • Low leukocyte alkaline phosphatase score Philadelphia chromosome is the most accurate test to distinguish

Answer 61

Abnormal fibrous deposition in bone marrow which = low blood count • Thought to be caused by hyperplasia of abnormal megakaryocytes [bone marrow cell responsible for the production of blood thrombocytes (platelets)] • The resultant release of platelet derived growth factor is thought to stimulate fibroblasts • Hematopoiesis develops in the liver and spleen

Answer 62

• E.g. Elderly person with symptoms of anemia e.g. Fatigue (the most common presenting symptom) • Massive splenomegaly • Hypermetabolic symptoms: weight loss, night sweats etc

Answer 63

• Anemia • High WBC and platelet count early in the disease • 'Tear-drop' poikilocytes on blood film • Unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed • High urate and LDH (reflect ↑ cell turnover) • leucoerythroblastic change

Answer 64

• Supportive care (blood transfusion, platelets, antibiotics) • Allogeneic stem cell transplantation in a select few • Splenectomy (CONTROVERSIAL)

Answer 65

occurs mainly in the elderly, 30% transforms to AML

Answer 66

•Anaemia • Infection • Bleeding = Due to pancytopenia

Answer 67

• Serial blood counts show evidence of increasing bone marrow failure • Bone marrow shows increased cellularity.

Answer 68

• < 5% blasts in the bone marrow → manage conservatively. • ↑ WBC → gentle chemotherapy. • < 60 years old → Intensive chemotherapy

Answer 69

The Philadelphia chromosome is present in more than 95% of patients with CML. It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34:q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal.

Answer 70

Presentation (40-50 years) • Middle-age • Anemia, weight loss • Splenomegaly may be marked (lethargy, anorexia, abdominal discomfort – 75% palpable spleen) • Hepatomegaly and lymphadenopathy are uncommon • Spectrum of myeloid cells seen in peripheral blood • ↓ neutrophil alkaline phosphatase • May undergo blast transformation (AML in 80%, ALL in 20%)

Answer 71

• Philadelphia is confirmatory • Peripheral blood film: (leukocytosis in all stages of differentiation within the myeloid linage) • Basophilia is important diagnostic marker especially when Philadelphia is absent • Monocytopenia • Bone-marrow hypercellularity with ↑ myloid-erythroid ratio ↑ Granulocytes of all types, typically including mature myeloid cells. Basophils and eosinophils are almost universally ↑; this feature may help differentiate CML from a leukemoid reaction. A bone marrow biopsy is often performed as part of the evaluation for CML, and CML is confirmed by detecting the Philadelphia chromosome, this can be detected by routine cytogenetics, by fluorescent in situ hybridization, or by PCR for the bcr-abl fusion gene.

Answer 72

• Hydroxyurea (also used in PRV, painful attacks in sicklers and as antiretroviral in HIV) • Interferon- α • Imatinib (inhibitor of tyrosine kinase) Inhibitor of the tyrosine kinase associated with the BCR-ABL defect, Very high response rate in chronic phase CML • Allogenic bone marrow transplant (optimum management)

Answer 73

Malignant disease of WBC’s and RBC’s

Answer 74

is the most common form of acute leukemia in adults. It mayoccur as a primary disease or following a secondary transformation of a myeloproliferative disorder(e.g CML, myelofibrosis). > 30% blasts are almost diagnostic of AML.

Answer 75

• Early signs are vague and non-specific (influenza-like) • Persistent or frequent infections (due to ↓ WBC) • Bruising and petechiae (due to ↓ PLT) • Splenomegaly may occur but typically mild and asymptomatic. Lymph node swelling is rare. Symptoms are caused by Pancytopenia (↓RBC - ↓WBC - ↓PLT)

Answer 76

The combination of a myeloperoxidase or Sudan black stain and a non-specific esterase (NSE) stain will provide distinction of AML from ALL and in subclassification of AML in most cases.

Answer 77

Chemotherapy: divided into two phases Induction and consolidation phases

Answer 78

Induction: All types except M3 are given induction with cytarabine (ara-C) and an anthracycline (such as daunorubicin or idarubicin).This regimen is known as "7+3", because the ara-C is given as a continuous IVI for 7 days while the anthracycline is given for 3 consecutive days as an IV push.

Answer 79

Consolidation: even after complete remission, very few leukemic cells likely to remain undetected with current diagnostic techniques. If no further post-remission therapy is given, almost all patients will eventually relapse. Therefore, more therapy is necessary to eliminate non-detectable disease and prevent relapse — that is, to achieve a cure. The specific type of postremission therapy is individualized based on prognostic factors and general health: For good-prognosis leukemias [t(8;21), and t(15;17)], patients will typically undergo an additional 3–5 courses of intensive chemotherapy For patients at high risk of relapse (e.g. those with high-risk cytogenetics, underlying MDS, or therapy-related AML), allogeneic stem cell transplantation is usually recommended

Answer 80

The first clue is typically an abnormal CBC. While ↑ WBC is a common finding, and leukemic blasts are sometimes seen, AML can also present with isolated ↓ PLT, ↓ RBCs, or even ↓ WBC. While a presumptive diagnosis of AML can be made via examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy. Auer rod: an esoinophilic needle like inclusion in cytoplasm of blast cells is pathgenomic of AML

Answer 81

• > 60 years • > 20% blasts after first course of chemo • Cytogenics: deletions of chromosome 5 or 7

Answer 82

+ve: M4 - Granulocytic and monocytic maturation strongly +ve: M5 - Monocytic

Answer 83

M6 - Erythroleukemia

Answer 84

Younger age around 25 Chest infection, ↑WBC and DIC or thrombocytopenia often at presentation

Answer 85

• Associated with t(15:17) • Fusion of PML and RAR-α genes

Answer 86

• Treated with the ATRA in addition to induction chemotherapy. Care must be taken to prevent DIC, complicating the treatment of APL when the promyelocytes release the contents of their granules into the peripheral circulation. APL

Answer 87

ATRA (all-trans-retinoic acid): activates the RAR- α gene thus helps the WBCs to differentiate (i.e mature) but it will not eliminate the leukemia.

Answer 88

is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)

Answer 89

• Often none • Constitutional: anorexia, weight loss • Bleeding, infections • Lymphadenopathy more marked than CML

Answer 90

• Hypogammaglobulinemia leading to recurrent infections → most common cause of death • Warm autoimmune hemolytic anemia in 10-15% of patients • Transformation to high-grade lymphoma (Richter's transformation)

Answer 91

• Immunophenotyping (flow cytmetry) Immunophenotyping will demonstrate the cells to be B-cells (CD19 positive). CD5 and CD23 are also characteristically positive in CLL • Blood film: smear or smudge cells

Answer 92

• Progressive marrow failure: the development or worsening of anemia and/or thrombocytopenia • Massive (>10 cm) or progressive lymphadenopathy • Massive (>6 cm) or progressive splenomegaly • Progressive lymphocytosis: > 50% ↑ over 2 months or lymphocyte doubling time < 6 months • Systemic symptoms: weight loss > 10% in previous 6 months, fever >38oc for > 2 weeks, extreme fatigue, night sweats • Autoimmune cytopenias e.g. ITP

Answer 93

• None early on (when to start Rx is mentioned above) • Chlorambucil to ↓ lymphocyte count • Other options include fludarabine (because fludarabine causes profound lymphopenia, thus increases the risk of opportunistic infections significantly, prior to commensing fludarabine you must give co-trimoxazole or to use monthly nebulised pentamidine to prevent Pneumocystis carinii pneumonia)

Answer 94

3-5 years • ♂ Sex • Age > 70 years • Lymphocyte count > 50 • Prolymphocytes comprising > 10% of blood lymphocytes • Lymphocyte doubling time < 12 months • Raised LDH • CD38 expression positive

Answer 95

Veno-Occlusive Disease (VOD) or Hepatic veno-occlusive disease. It is a complication of high-dose chemotherapy given before a bone marrow transplant (BMT). The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation. Treatment is primarily supportive.

Answer 96

Features: • Fluid retention (weight gain, generalized edema, pleural effusion) • Hepatomegaly • ↑ Bilirubin (Jaundice) • Usually complicated by multi-organ failure

Answer 97

Diagnosis: • U/S abdomen helps in diagnosis • Liver biopsy shows centrolobar necrosis

Answer 98

is a rare malignant proliferation disorder of B cells lymphocytes. It is more common in ♂s (4:1) and is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cells are abnormal WBCs with hair-like projections of cytoplasm.

Answer 99

• Pancytopenia (Monocytopenia is classical) • Splenomegaly • Skin vasculitis in 1/3 patients • 'Dry tap' despite bone marrow hypercellularity (also seen in myelofibrrosis) • Bone marrow biopsy migh show "fried egg appearance" • Tartrate resistant acid phosphotase (TRAP) stain positive Lymphadenopathy is very uncommon in hairy cell leukaemia

Answer 100

• Chemotherapy is first-line: cladribine, pentostatin • Immunotherapy is second-line: rituximab, interferon-α • Splenectomy sometimes required

Answer 101

Acute lymphoblastic leukaemia Malignant disease of lymphocytes (can also infiltrate lymph nodes) causes damage and death by crowding out normal cells in the bone marrow, and by metastasizing. ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age.

Answer 102

The overall cure rate in children is ≈80%, and ≈45%-60% of adults have long-term disease-free survival. Acute → relatively short course of the disease (being fatal in as little as a few weeks if untreated)

Answer 103

• Generalized weakness and fatigue • Anemia • Frequent or unexplained fever and infections • Weight loss and/or loss of appetite • Excessive and unexplained bruising • Bone pain, arthralgia. • Dyspnea due to lung infiltration. • Lymphandeopathy, hepatosplenomegaly. • Pitting edema in the lower limbs and/or abdomen • Petechiae due to thrombocytopenia The signs and symptoms of ALL are variable but follow from bone marrow infiltration and/or organ infiltration.

Answer 104

t(12:21) is the most common translocation and portends a good prognosis. Philadelphia chromosome t(9:22) also has a bad prognosis. t(4:11) is the most common in children under 12 months and portends a poor prognosis.

Answer 105

• Leukocytosis. • Blast cells are seen on blood smear in 90% of cases • Bone marrow biopsy is conclusive proof of ALL • LP to detect CNS involvement. • CXR: to look for mediastinal mass (common in ALL). • U&E to look for Tumor Lysis Syndrome. • Immunophenotyping, establish whether the "blast" cells origin is B or T lymphocytes • DNA testing; different mutations reflect prognosis. Terminal Deoxynucleotide Transferase (TdT) is present in 95% of ALL

Answer 106

Before treating with chemotherapy, if blast cell count is very ↑ (>100 x 109/L), the patient needs Leukapheresis to prevent sludging of capillary beds, this can be life-saving

Answer 107

Good prognostic factors • Common ALL • Pre-B phenotype • Low initial WBC • FAB L1 type

Answer 108

Poor prognostic factors • FAB L3 type • T or B cell surface markers • Philadelphia translocation, t(9;22) • Age < 2 years or > 10 years • ♂ Sex. • CNS involvement • High initial WBC (e.g. > 100 * 109/l) • Non-Caucasian

Answer 109

Any anemic condition resulting from space-occupying lesions in the bone marrow; the circulating blood contains immature cells of the granulocytic series and nucleated red blood cells, frequently in numbers that are disproportionately large in relation to the degree of anemia. (left-shifted granulocytic series and nucleated red blood cells) with pancytopaenia. Also defined when there are immature cells (e.g myelocytes, and nucleated red blood cells) seen on the peripheral blood film.

Answer 110

• ↑ Bone marrow turnover e.g. in severe hemolytic anemia (in which case the reticulocyte count would be high). • Myelofibrosis and Chronic Myeloid Leukaemia (where there would be splenomegaly, and the white cell and platelet count would usually be raised). • Bone marrow invasion. Often in bone marrow invasion the invading malignancy will already have been diagnosed previously. • Myeloma • Polycythaemia Rubra Vera • Osteopetrosis • Tuberculous infiltration of the bone marrow • Sarcoidosis

Answer 111

is a malignant proliferation of lymphocytes characterized by the presence of the Reed-Sternberg cell.

Answer 112

It has a bimodal age distributions being most common in the third and seventh decades.

Answer 113

Hodgkin’s lymphoma is associated with EBV.

Answer 114

25% of patients have a constitutional upset, (night sweats, weight loss, fever, pruritus and lethargy)

Answer 115

Ann-Arbor staging of Hodgkin's lymphoma • I: single lymph node • II: 2 or more lymph nodes/regions on same side of diaphragm • III: nodes on both sides of diaphragm • IV: spread beyond lymph nodes

Answer 116

Each stage may be subdivided into A or B • A = no systemic symptoms other than pruritus • B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)

Answer 117

• Age = 45 years • Stage IV disease • Hemoglobin < 10.5 g/dl • Lymphocyte count < 600/μl or < 8% • ♂ • Albumin < 40 g/l • White blood count = 15,000/μl

Answer 118

Classical Hodgkin's lymphoma (excluding nodular lymphocyte predominant Hodgkin's lymphoma) can be subclassified into 4 pathologic subtypes based upon Reed-Sternberg cell morphology and the composition of the reactive cell infiltrate seen in the lymph node biopsy specimen (the cell composition around the Reed-Stenberg cell(s)).

Answer 119

nodular sclerosing mixed-cellularity subtype lymphocyte rich lymphocyte depleted

Answer 120

Is the most common subtype and is composed of large tumor nodules showing scattered lacunar classical RS cells set in a background of reactive lymphocytes, eosinophils and plasma cells with varying degress of collagen fibrosis/sclerosis.

Answer 121

Is a common subtype and is composed of numerous classic RS cells admixed with numerous inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells. Without sclerosis. This type is most often associated with EBV infection and may be confused with the early, so-called 'cellular' phase of nodular sclerosing CHL. Good Prognosis

Answer 122

Is a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte predominant B-cell Non-Hodgkin's (B-NHL). Best Prognosis

Answer 123

Is a rare, the least subtype, composed of large numbers of often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously classified within this category would now be reclassified under anaplastic large cell lymphoma. Worse Prognosis

Answer 124

Nodular lymphocyte predominant Hodgkin's lymphoma expresses CD20, and is not currently considered a form of classical Hodgkin's → Remember, Rituximab is anti-CD20.

Answer 125

• Hodgkin results in patchy bone marrow infiltration, an isolated bone marrow biopsy may yield non-specific results. • Bone marrow biopsy is more useful for staging of advanced disease. • Lymph node biopsy would be more likely to be positive, Reed-Sternberg cell is evident on microscopy

Answer 126

• Early stage (IA or IIA) are effectively treated with radiation therapy AND chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. • Later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. • Large mass in the chest (regardless of stage) are usually treated with combined chemotherapy and radiation therap. Chemo includes: Doxorubicin, Bleomycin, Vincristine, Cyclophosphamide and other cytotoxic drugs.

Answer 127

are a diverse group of lymphomas that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive. Low-grade lymphoma is predominantly a disease of older people. Most non-Hodgkin’s lymphomas are of B cell phenotype, though T cell tumours are increasingly being recognized.

Answer 128

• Most present with advanced disease, bone marrow infiltration being almost invariable. • Burkitt’s lymphoma is a high-grade lymphoma, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement and ovarian tumours. • Extra-nodal presentation is more common than Hodgkin's disease. • Renal impairment in non-Hodgkin’s lymphomas usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement. • Anaemia, an elevated white cell count and/or thrombocytopaenia are suggestive of bone marrow infiltration.

Answer 129

• Lymph node biopsy is sufficient for a definitive diagnosis. • It is essential for modern classification to submit the lymphoid tissue for immuno-phenotyping and cytogenetic/molecular analysis.

Answer 130

• High-grade lymphomas are responsive to chemotherapy and potentially curable, • Low-grade lymphomas are incurable with conventional therapy. • Chemotherapy is the mainstay of treatment in most cases.

Answer 131

This occurs after the initiation of a chemotherapeutic. TLS tends to occur in patients with bulky, rapidly proliferating, treatment-responsive tumors

Answer 132

• Acute leukemia • High-grade non-Hodgkin’s lymphomas. • Pre-treatment ↑ LDH (levels of LDH correspond with tumor bulk)

Answer 133

• Prevention is with good hydration before starting chemotherapy. • ↑ uricemia → urine alkalinisation and allopurinol • Osmotic diuretics are NOT first line therapy and may contribute to the precipitation of uric acid in the renal tubules. • Dietary modifications include restricting dietary potassium. • Further chemotherapy should be withheld until the patient has fully recovered

Answer 134

• Present in > 95% of patients with CML • This results in part of the Abelson (ABL) proto-oncogene being moved to the BCR gene on chromosome 22 • The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal • Poor prognostic indicator in ALL and AML

Answer 135

• Seen in acute promyelocytic leukemia (M3) • Fusion of PML and RAR-α genes

Answer 136

• Seen in Burkitt's lymphoma • MYC oncogene is translocated to an immunoglobulin gene

Answer 137

• Mantle cell lymphoma • Deregulation of the cyclin D1 (BCL-1) gene

Answer 138

Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma

Answer 139

High-grade B-cell lymphoma

Answer 140

Adult T-cell leukemia/lymphoma

Answer 141

gastric lymphoma (MALT)

Answer 142

Burkitt's lymphoma

Answer 143

Stem cell transplants from unrelated or haploidentical donors are not used in first complete remission in most adult hematological malignancies due to the high treatment related mortality/morbidity: they are reserved for first relapse/second complete remission.

Answer 144

Stem cell transplants from matched sibling donors are used as first line therapy in certain circumstances, including chronic myeloid leukaemia.

Answer 145

Irradiated blood is required in patients receiving a bone marrow transplant, patients with previous purine analogue exposure and a diagnosis of Hodgkin’s disease.

Answer 146

Cytomegalovirus (CMV)-negative blood should be used in patients who may need a bone marrow transplant in the future (since carriage of CMV increases transplant mortality).

Answer 147

If patient had siblings then related stem cell transplant may be considered. in the absence of siblings, imatinib to induce remission is the initial therapy of choice in patient with no siblings. Imatinib mesylate used as first line therapy brings about complete cytogenetic remissions in 76% of patients, with some patients becoming negative by polymerase chain reaction for the 9:22 translocation. It is not however thought to be curative, and young patients with a sibling donor are still referred for transplantation.

Answer 148

• Asthma • Allergic bronchopulmonary aspergillosis • Churg-strauss syndrome • Loffler's syndrome • Tropical pulmonary eosinophilia • Eosinophilic pneumonia • Hypereosinophilic syndrome

Answer 149

• Schistosomiasis • Nematodes: Toxocara, Ascaris, Strongyloides • Cestodes: Echinococcus

Answer 150

sulfasalazine, nitrofurantoin

Answer 151

Neoplasia, Addison Disease, Allergy/Asthma, Collagen Vascular diseases, Cholesterol emboli, and parasites.

Answer 152

rare unknown cause disease, occurring most commonly in ♂ in the 30-40-year-age group with persistent and markedly raised peripheral blood eosinophil count.

Answer 153

• Lung involvement may occur • Cardiovascular involvement with fibrosis and restrictive cardiomyopathy, which may lead to mural thrombus formation and considerable morbidity and mortality. • Angioedema or urticaria.

Answer 154

is with high dose corticosteroids (e.g. prednisolone 50mg which leads to a response in around 50% of cases). Steroid sparing agents such as cyclophosphamide or azathioprine may also be of some value.

Answer 155

Prothrombin time - prolonged Activated Partial thromboplastin time - prolonged Bleeding time- normal

Answer 156

2 7 9 and 10, and protein C and protein S are all vit K dependant to be activated

Answer 157

λ Poor dietary intake λ Malabsorption λ Obstructive jaundice – bile salts can’t get into the gut λ Vitamin K antagonists (warfarin) λ Haemorrhagic disease of the newborn

Answer 158

all prolonged

Answer 159

Prothrombin time - normal Activated Partial thromboplastin time -prolonged Bleeding time - normal

Answer 160

PT prolonged APTT normal

Answer 161

both prolonged

Answer 162

PT normal APTT prolonged

Answer 163

Factor VII deficiency is very rare, is inherited in an autosomal recessive fashion, and tends to cause a mild/moderate bleeding disorder, although the phenotype does vary.

Answer 164

Treatment is by factor replacement with plasma-derived products or using recombinant activated factor VII.

Answer 165

When an abnormality is detected in the PT/APTT the studies are repeated with a 50:50 mix of test and normal plasma: straightforward factor deficiencies will correct with mixing, but inhibitors (most commonly lupus anti-coagulant) do not correct. It should be noted however that the results of PT mixing studies in patients on warfarin are consistent with factor deficiencies, because warfarin acts as an anti-coagulant by decreasing the activity of factors II, VII, IX, and X.

Answer 166

results from the development of inhibitors against factor VIII coagulation factor. It occurs mainly in elderly.

Answer 167

• Bleeding tendencies • APTT: is prolonged (intrinsic pathway). • APTT doesn’t correct/will only correct slightly with the adding of normal plasma. • Bethesda titre can quantify the inhibitor. There is a 20% mortality rate from acquired factor VIII deficiency.

Answer 168

• Replacement of factor VIII is usually ineffective as the inhibitor has rapid activity. • Bleeding can be treated with recombinant activated factor VII or Factor Eight Bypassing Agent (FEIBA), but the latter is a pooled donor product and is pro-thrombotic, causing myocardial infarctions and DIC in a subset of patients. • rFVIIa has been successfully used in patients with acquired hemophilia. It binds to the surface of activated platelets, where it supports thrombin generation and bypasses the need for FVIII. • Definitive removal of the auto-antibody: immunosuppression is successful in at least half of patients, but carries significant morbidity and mortality in the elderly

Answer 169

Activated protein C resistance (Factor V Leiden) is the most common inherited thrombophilia

Answer 170

It is due to a mutation in the Factor V Leiden gene. Heterozygotes have a 5-fold risk of venous thrombosis whilst homozygotes have a 50-fold ↑ risk. Any white pt aged <45 with thrombotic event should make you think of factor V Leiden mutation.

Answer 171

Von Willebrand's disease is the most common inherited bleeding disorder

Answer 172

The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst hemoarthroses and muscle hematomas are rare.

Answer 173

• Large glycoprotein which forms massive multimers up to 1,000,000 Da in size • Promotes platelet adhesion to damaged endothelium • Carrier molecule for factor VIII

Answer 174

type 1: partial reduction in vWF (80% of patients) type 2: abnormal form of vWF type 3: total lack of vWF (autosomal recessive)

Answer 175

• Petechial skin • Slightly elevated APTT • ↓ factor VIII activity

Answer 176

• Prolonged bleeding time • APTT may be prolonged • Factor VIII levels may be moderately ↓ • Defective platelet aggregation with ristocetin

Answer 177

• Tranexamic acid for mild bleeding • Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells. Used as prohyplaxis prior to procedures. • Factor VIII concentrate

Answer 178

• ITP • TTP • DIC • Hematological malignancy

Answer 179

Causes of moderate thrombocytopenia • Heparin induced thrombocytopenia (HIT) • Drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides) • Alcohol and Vitamin B12 deficiency • Liver disease • Hypersplenism • Viral infection (EBV, HIV, hepatitis) • Pregnancy • SLE/antiphospholipid syndrome

Answer 180

is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex.

Answer 181

♀:♂=2.6:1.

Answer 182

Common cause of death is bleeding (mainly intracranial).

Answer 183

• Antiplatelet autoantibodies (usually IgG) • Bone marrow aspiration shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukemia

Answer 184

Acute and chronic

Answer 185

Acute ITP o More commonly seen in children o Equal sex incidence o May follow an infection or vaccination o Usually runs a self-limiting course over 1-2 weeks

Answer 186

o More common in young/middle-aged women o Tends to run a relapsing-remitting course

Answer 187

• ITP in association with autoimmune hemolytic anemia (AIHA)

Answer 188

• Abnormally large and sticky multimers of vWF cause platelets to clump within vessels • In TTP there is a deficiency of caspase which breakdowns large multimers of vWF. • Overlaps with hemolytic uraemic syndrome (HUS)

Answer 189

• Rare, typically adult ♀ • Fever • Fluctuating neuro signs (microemboli) • Microangiopathic hemolytic anemia • Thrombocytopenia • Renal failure

Answer 190

Neuro signs and purpura point towards TTP

Answer 191

• Post-infection e.g. Urinary, gastrointestinal • Pregnancy • Drugs: cyclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir • Tumors • SLE • HIV

Answer 192

• No antibiotics - may worsen outcome • Plasma exchange is the treatment of choice • Steroids, immunosuppressants • Vincristine The management of thrombotic thrombocytopenic purpura involves steroids and immunosuppressants. Plasma exchange is the treatment of choice

Answer 193

is a severe immune-mediated drug reaction that can occur in patients receiving unfractionated heparin (at full therapeutic doses and low prophylactic doses, including the minute amounts in heparin flushes and on heparin-coated catheters) and those receiving low-molecular weight heparin (LMWH). Antibodies usually develop after a patient has been on heparin for five or more days, but may develop sooner if there has been previous heparin exposure.

Answer 194

Despite thrombocytopenia, bleeding is rare. HIT is strongly associated with thrombosis. Thromboembolic complications can be venous, arterial, or both, and include: • DVT • Pulmonary embolism • Myocardial infarction • Thrombotic stroke • Occlusion of limb arteries. (HIT predisposes to thrombosis (the abnormal formation of blood clots inside a blood vessel) because platelets release microparticles that activate thrombin, thereby leading to thrombosis. When thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT).)

Answer 195

• Type I: usually occurs 48 to 72 hours post commensing heparing and PLT rarely < 100. PLT returns to normal over 4 days and there is no ↑ risk of thromboembolism • Type II: much rarer and usually occurs 5 to 10 days after starting heparin, PLT usually <100, patients are at ↑ risk of thromboembolic events. Heparin products should be stopped and the patient commenced on alternative medication

Answer 196

• Stop all forms of Heparin • Start alternative anticoagulant which do not cross-react with HIT antibodies, such as: o Danaparoid o Lepirudin o Argatroban. • Oral anticoagulation with warfarin should NOT be initiated for longer-term protection from further events until substantial platelet count recovery has occurred. HIT patients who are switched to warfarin alone after the discontinuation of heparin may paradoxically have worsening thrombosis and develop venous limb gangrene and skin necrosis. -initiate on suspicion before confirming diagnosis

Answer 197

clinical diagnosis • Thrombocytopenia: PLT < 100 or <50% from the patient's baseline • The exclusion of other causes of thrombocytopenia • The resolution of thrombocytopenia after cessation of heparin. • Supportive lab tests: HIT antibodies can be demonstrated in vitro by functional tests (are more specific) and immunoassays. Functional tests; measure platelet activity in the presence of the patient's serum and heparin include: o Heparin Induced Platelet Aggregation (HIPA) o Serotonin Release Assay (SRA)

Answer 198

• Target cells • Howell-Jolly bodies • Cabot's rings • Siderotic granules • Acanthocytes • Schizocytes

Answer 199

• Target cells • 'Pencil' poikilocytes • If combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells

Answer 200

• koilonychia • atrophic glossitis • post-cricoid webs • angular stomatitis

Answer 201

Heinz bodies Bite and blister cells may also be seen

Answer 202

myelofibrosis

Answer 203

intravascular haemolysis

Answer 204

megaloblastic anaemia

Answer 205

Splenic lymphoma with villous lymphocytes

Answer 206

Follicular lymphoma

Answer 207

Always +ve in hairy cell leukaemia

Answer 208

acute myeloblastic leukaemia

Answer 209

acute lymphoblastic leukaemia

Answer 210

↑ in polycythemia RV and myelofibrosis ↓ in chronic myeloid leukaemia

Answer 211

Also known as Osler-Weber-Rendu syndrome, hereditary hemorrhagic telangiectasia is an autosomal dominant condition characterized by (as the name suggests) multiple telangiectasia over the skin and mucous membranes. 20 % of cases occur spontaneously without prior family history.

Answer 212

5 are identified HHT1 to HHT4 and JPHT (HHT and juvenile polyposis)

Answer 213

• HHT1: chromosome 9, associated with ↑ AVM (cerebral and pulmonary) • HHT2: chromosome 12.

Answer 214

• Epistaxis • Telangiectasia develop ob skin, mucous membranes and internal organs • Associated with pulmonary and other AV malformations in 10% • May present as iron-deficiency anemia secondary to bleeding in the GI tract or nasal mucosa

Answer 215

It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein older men systemic upset: weight loss, lethargy hyperviscosity syndrome e.g. visual disturbance the pentameric configuration of IgM increases serum viscosity hepatosplenomegaly lymphadenopathy cryoglobulinaemia e.g. Raynaud's high ESR

Answer 216

• Alkylating agents • Young patient may benefit from doxorubicin. • Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or Vincristine or with thalidomide. • Corticosteroids, such as Prednisone, may also be used in combination. • Plasmapheresis can be used to treat the hyperviscosity (it does not address the underlying disease)

Answer 217

• Usually asymptomatic • No bone pain or ↑ risk of infections • Around 10-30% of patients have a demyelinating neuropathy • M protein level < 30gm/l • No end-organ damage.

Answer 218

• Normal immune function • Normal β-2 microglobulin levels • Lower level of paraproteinemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA) • Stable level of paraproteinemia • No clinical features of myeloma (e.g. Lytic lesions on x-rays or renal disease) One of the key differentiating features between (MGUS) and myeloma is the absence of complications such as immune paresis, hypercalcemia and bone pain

Answer 219

• Serum paraprotein <30 g/L AND • Clonal plasma cells <10% on bone marrow biopsy AND • NO myeloma-related organ or tissue impairment

Answer 220

Methemoglobinemia = oxidation of Fe2+ in hemoglobin to Fe3+ describes hemoglobin which has been oxidised from Fe++ (Ferrous) to Fe+++. This is normally regulated by NADH methemoglobin reductase, which transfers electrons from NADH to methemoglobin resulting in the reduction of methemoglobin to hemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

Answer 221

• Hemoglobin chain variants: HbM, HbH • NADH methemoglobin reductase deficiency

Answer 222

• Drugs: sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine • Chemicals: aniline dyes

Answer 223

• 'Chocolate' cyanosis • Dyspnea, anxiety, headache • Severe: acidosis, arrhythmias, seizures, coma • Normal PO2 but ↓ oxygen saturation

Answer 224

• NADH - methemoglobinemia reductase deficiency: ascorbic acid • IV methylene blue if acquired

Answer 225

• Autosomal recessive • Aplastic anemia • ↑ risk of AML • Neurological manifestation • Skeletal abnormalities • Skin pigmentation (café-au-lait spots)

Answer 226

is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. *there are rare cases of families with classic features of genetic hemochromatosis but no mutation in the HFE gene

Answer 227

Hemochromatosis is the most prevalent genetic condition in Caucasian population with a carrier rate of 1 in 10 and is present in about 1 in 200-400 people. Cystic fibrosis (CF) has a carrier rate of 1 in 25 and is present in about 1 in 2,500 births. CF is often quoted as being the most common lethal inherited condition in Caucasians

Answer 228

• General population: transferrin saturation is considered the most useful marker. Ferritin should also be measured but is not usually abnormal in the early stages of iron accumulation • Testing family members: genetic testing for HFE mutation • These guidelines may change as HFE gene analysis become less expensive

Answer 229

• Molecular genetic testing for the C282Y and H63D mutations • Liver biopsy: Perl's stain

Answer 230

Typical iron study profile in patient with hemochromatosis • Transferrin saturation > 55% in men or > 50% in women • Raised ferritin (e.g. > 500 ug/l) and iron • Low TIBC

Answer 231

• BSCH recommend 'transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l'

Answer 232

Presenting features • Early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) • 'Bronze' skin pigmentation • Diabetes Mellitus • Liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition. • Cardiac failure (2nd to dilated cardiomyopathy) • Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) • Arthritis (especially of the hands) Joint x-rays characteristically show chondrocalcinosis

Answer 233

• Cardiomyopathy • Skin pigmentation

Answer 234

• Liver cirrhosis** • Diabetes mellitus • Hypogonadotrophic hypogonadism • Arthropathy **whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not

Answer 235

Following a splenectomy patients are particularly at risk from pneumococcus, Hemophilus, meningococcus and Capnocytophaga canimorsus (usually from dog bite) infections

Answer 236

• If elective, should be done 2 weeks prior to operation • Pneumococcal, HIB, meningitis A & C and annual influenza vaccination

Answer 237

• Penicillin V: unfortunately clear guidelines do not exist of how long antibiotic prophylaxis should be continued. It is generally accepted though that penicillin should be continued for at least 2 years and at least until the patient is 16 years of age, although the majority of patients are usually put on antibiotic prophylaxis for life

Answer 238

• Splenectomy • Sickle-cell • Coeliac disease, dermatitis herpetiformis (HLA DR3) • Graves' disease • SLE • Amyloid

Answer 239

o Autoimmune attack against haemopoietic stem cell (therefore no haemopoiesis)

Answer 240

This shows an aplastic anaemia pt’s bone marrow where cells or clusters of cells can’t be seen because they’ve been replaced by fat.

Answer 241

Supportive • Blood products • Prevention and treatment of infection Anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) • Prepared in animals (e.g. Rabbits or horses) by injecting human lymphocytes • Is highly allergenic and may cause serum sickness (fever, rash, arthralgia), therefore steroid cover usually given • Immunosuppression using agents such as Cyclosporin may also be given Stem cell transplantation • Allogeneic transplants have a success rate of up to 80%

Answer 242

• Vitamin B12 deficiency • Folate deficiency • Cytotoxics e.g. Hydroxyurea

Answer 243

It is important in a patient who is also deficient in both vitamin B12 and folic acid to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

Answer 244

• Alcohol • Liver disease • Hypothyroidism • Pregnancy • Reticulocytosis e.g. Hemolysis • Aplastic anemia • Myelodysplasia • Drugs: cytotoxics

Answer 245

ν Tetramer made up of 2 alpha globin like chains and 2 beta globin like chains ν One haem group attached to each globin chain Each copy of chromosome 16 has two genes for the alpha globin subunit (four in total), and each copy of chromosome 11 has one gene for the beta subunit (two in total).

Answer 246

ν Hereditary disorders of globin chain synthesis resulting in impaired haemoglobin production Ð Alpha thalassaemia; α chains affected Ð Beta thalassaemia; β chains affected ν Inadequate Hb production → microcytic hypochromic anaemia ν Unbalanced accumulation of globin chains → ineffective erythropoiesis and haemolysis

Answer 247

2 separate α-globulin genes are located on each chromosome 16

Answer 248

silent alpha thalassaemia trait -no symptoms

Answer 249

α thal trait; two affected genes (--/αα or -α/-α) ν Microcytic, hypochromic red cells with mild anaemia ν Important as can be mistaken for iron deficiency ( but normal ferritin, raised red cell count) ν Red cell inclusions (HbH bodies) can sometimes be seen with special stains (golf ball cells)

Answer 250

HbH disease ν Severe form of α thalassaemia ν Only 1 working α gene per cell (--/-α ) ν α chain production < 30% of normal ν Anaemia (Hb 30-130g/l) with very low MCV and MCH ν Due to globin chain imbalance, excess β chains form tetramers (β4), called HbH, which cannot carry oxygen ν HbH present in variable amounts (1-40%) Extramedullary haematopoeisis: hepatosplenomegaly, englarged bone marrow,

Answer 251

ν Mild: transfusion only needed at times of intercurrent illness ν Severe cases transfusion dependent ν Splenectomy may reduce transfusion need in severe cases (NB vaccinations) ν Folic acid supplementation (↑ RBC turnover so ↑demand)

Answer 252

If all 4 α chains absent (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)

Answer 253

intrauterine blood transfusion followed by bone marrow transplant

Answer 254

ν Disorder of beta chain synthesis ν Reduced ( β+), or absent ( β0 ) beta chain production ν Only β chains and hence only HbA (α2β2) affected ν Usually caused by point mutations (opposite of alpha thal) ν Over 200 mutations identifed so far ν Autosomal recessive inheritance

Answer 255

β thalassaemia trait (usually β+ /β or β0/ β); ν Asymptomatic ν Low MCV/MCH ν Raised HbA2 is diagnostic

Answer 256

ν β thalassaemia intermedia (usually β+ /β+ or β0 /β+); ν Moderate severity requiring occasional transfusion

Answer 257

ν β thalassaemia major; ν Severe, lifelong transfusion dependency

Answer 258

ν Moderate to severe anaemia (Hb 30-90g/l) ν Very low MCV/MCH ν Reticulocytosis ν Film; anisopoikilocytosis and target cells (lack of central pallor) ν HPLC: Ð mainly HbF present Ð small amounts of HbA Ð HbA2 often elevated

Answer 259

ν Presents aged 6-24 months (adult Hb affected) ν Failure to thrive ν Pallor Extramedullary haematopoiesis causing; ν Hepatosplenomegaly ν Skeletal changes – more haematopoiesis in bone medulla causes it to increase in size ν Organ damage 'hair on end' appearance of bone

Answer 260

Hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts of India; clinically similar to β thalassemia major or thalassemia intermedia.

Answer 261

Hemoglobin S/thalassemia, common in African and Mediterranean populations; clinically similar to sickle cell anemia, with the additional feature of splenomegaly

Answer 262

Hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/βo thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β+ thalassemia produce a milder disease.

Answer 263

Inhibits formation of microtubules, mitotsis inhibitor (M stage of cell cycle) Peripheral neuropathy (reversible)

Answer 264

Causes Cross-linking in DNA Ototoxicity, peripheral neuropathy, hypomagnesaemia

Answer 265

Degrades preformed DNA Lung fibrosis

Answer 266

Stabilizes DNA-topoisomerase II complex. Inhibits DNA & RNA synthesis Cardiomyopathy

Answer 267

Inhibits dihydrofolate reductase and thymidylate synthesis Myelosuppression, mucositis

Answer 268

Alkylating agent - causes Cross-linking in DNA Hemorrhagic cystitis (incidence ↓by the use of hydration and mesna), myelosuppression, transitional cell carcinoma

Answer 269

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin Neutropaenia + peripheral neuropathy

Answer 270

Inhibitor of the tyrosine kinase associated with the BCR-ABL defect →CML Edema, nausea, rash and musculoskeletal pain are common but mild. Severe congestive cardiac failure is an uncommon but recognized side effect

Answer 271

Cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-α and IFN-β bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors. IFN-α is produced by leucocytes and has an antiviral action USES: CML, Hairy cell Leukemia, hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer. The most frequent adverse effects are flu-like symptoms and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy causes immunosuppression, in particular through neutropenia and can result in some infections manifesting in unusual ways

Answer 272

extravasation should be suspected if a patient complains of pain, burning, swelling or redness at the site of the infusion cannula. • Immediate management would consist of stopping the infusion, immobilizing the arm and attempting to aspirate any accessible drug from the cannula and extravasation site before removal of the cannula. • Agent specific antidotes can be given after receiving specialist advice. Cold compresses are generally applied except in the case of vinca alkaloids in which case a heat compress should be applied. • Doxorubicin or daunorubicin extravasation injuries are particularly prone to causing ulceration, particularly on the back of the hand and hence a plastic surgery consultation is likely to be needed, Use topical corticosteroids to treat the site of inflammation.Consider reporting to the National Extravasation Information Service.

Answer 273

Ovarian cancer

Answer 274

Pancreatic cancer

Answer 275

Breast cancer

Answer 276

Prostatic carcinoma

Answer 277

Hepatocellular carcinoma, teratoma

Answer 278

Colorectal cancer

Answer 279

Liver - (hepatocellular carcinoma)

Answer 280

Bladder (transitional cell carcinoma)

Answer 281

Mesothelioma and bronchial carcinoma

Answer 282

Oesophageal and gastric cancer

Answer 283

Hepatic angiosarcoma

Answer 284

Nausea and vomiting are common side-effects of chemotherapy. Risk factors for the development of symptoms include: anxiety age less than 50 years old concurrent use of opioids the type of chemotherapy used

Answer 285

For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line. For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone

Answer 286

Human papilloma virus (HPV) infection is the most important risk factor for developing cervical cancer. Subtypes 16,18 & 33 are particularly carcinogenic. The other most common subtypes (6 & 11) are non-carcinogenic and associated with genital warts.

Answer 287

Infected endocervical cells may undergo changes resulting in the development of koilocytes. These have the following characteristics: enlarged nucleus irregular nuclear membrane contour the nucleus stains darker than normal (hyperchromasia) a perinuclear halo may be seen

Answer 288

The ECOG score is a 'performance status' scale, or a score that measures the functional status a patient. It is used to decide if a patient is a good or poor candidate for future oncological therapies. Those with a poor functional status is a poor candidate for further chemotherapy.

Answer 289

0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours 3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours 4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 5 Dead

Answer 290

This patient has Meig's syndrome - an ovarian fibroma associated with a pleural effusion and ascites

Answer 291

Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase) Myelosuppression, mucositis, dermatitis

Answer 292

Purine analogue that is activated by HGPRTase, decreasing purine synthesis Myelosuppression

Answer 293

Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase Myelosuppression, ataxia

Answer 294

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA Myelosuppression

Answer 295

Tamoxifen is a SERM which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer.

Answer 296

menstrual disturbance: vaginal bleeding, amenorrhoea hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects venous thromboembolism endometrial cancer

Answer 297

Anastrozole and letrozole are aromatase inhibitors that reduces peripheral oestrogen synthesis. This is important as aromatisation accounts for the majority of oestrogen production in postmenopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.

Answer 298

osteoporosis NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer hot flushes arthralgia, myalgia insomnia

Answer 299

abdominal pain peripheral neuropathy (mainly motor) fatigue constipation blue lines on gum margin (only 20% of adult patients, very rare in children)

Answer 300

the blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant full blood count: microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased) in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Answer 301

Management - various chelating agents are currently used: dimercaptosuccinic acid (DMSA) D-penicillamine EDTA dimercaprol

Answer 302

B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis. Low levels of albumin are also associated with a poor prognosis

Answer 303

I B2 microglobulin < 3.5 mg/l Albumin > 35 g/l 62 mths median survival II Not I or III 45mths median survival III B2 microglobulin > 5.5 mg/l 29

Answer 304

Protein C deficiency is an autosomal codominant condition which causes an increased risk of thrombosis

Answer 305

venous thromboembolism skin necrosis following the commencement of warfarin: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis

Answer 306

Hereditary angioedema is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH) protein. C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Answer 307

• C1-INH level is low • Low C2 and C4 levels are seen, even between attacks

Answer 308

• Attacks may be proceeded by painful macular rash • Painless, non-pruritic swelling of subcutaneous/submucosal tissues • May affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral edema) • Urticaria is not usually a feature

Answer 309

• Acute: IV C1-inhibitor concentrate or FFP • Anabolic steroid; Danazol may help

Answer 310

is associated with anti-factor VIII IgG antibodies and is idiopathic in the majority of cases.

Answer 311

• Autoimmune diseases: (Rheumatoid Arthritis or IBD) • Drugs such as phenytoin.

Answer 312

• Where there are ↓ anti-factor VIII antibodies, factor VIII replacement may be all that is required. • Where bleeding is a serious problem then immunosupression with corticosteroids +/- steroid sparing agents such as cyclosporine may be required.

Answer 313

Wiskott-Aldrich syndrome causes primary immunodeficiency due to a combined B- and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to be caused by mutation in the WASP gene.

Answer 314

recurrent bacterial infections (e.g. Chest) eczema thrombocytopaenia low IgM levels

Answer 315

• Thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency • Polycythemia • Paroxysmal nocturnal hemoglobinuria • Hyperviscosity syndrome

Answer 316

Autoimmune • Antiphospholipid syndrome • Behcet's

Answer 317

Drugs • Combined oral contraceptive pill: 3rd generation more than 2nd generation • Antipsychotics (especially olanzapine) have recently been shown to be a risk factor

Answer 318

• Abnormality in enzymes responsible for the biosynthesis of heme. • Results in overproduction of intermediate compounds (porphyrins) • All Porphyrias has autosomal dominant inheritance excpet congenital porphyrias (recessive) • May be acute or non-acute

Answer 319

• Urinary porphyria is ↑ in all the 3 types • Fecal porphyria is ↑ in Variegate porphyria and hereditary porphyrias

Answer 320

• All porphyrias are photosensitive except AIP

Answer 321

• Autosomal dominant • Defect in porphobilinogen deAminase • Results accumulation of delta aminolaevulinic acid and porphobilinogen

Answer 322

• ♀s, 20-40 year olds more likely to be affected (♀5:1)

Answer 323

• Abdominal: abdominal pain, vomiting • Neurological: motor neuropathy • Psychiatric: e.g. Depression • Hypertension and tachycardia common • No feces porphyria (can not be detected in stool) • Typically present with abdominal symptoms, neuropsychiatric symptoms • Hypertension and tachycardia common • Urine turns deep red on standing

Answer 324

Diagnosis • Classically urine turns deep red on standing • Raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks) • Assay of red cells for porphobilinogen deaminase • Raised serum levels of delta aminolaevulinic acid and porphobilinogen

Answer 325

• Hematin: needs to be given very early in an attack to be effective. Effectiveness varies among individuals. They are not curative drugs, but can shorten attacks and reduce the intensity of an attack

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• Most common hepatic porphyria • 80% sporadic and 20% autosomal dominant • No neurological consequences only urine porphyria • The exact frequency is not clear because many people with PCT never experience symptoms • Defect in uroporphyrinogen decarboxylase

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• May be caused by hepatocyte damage e.g. Alcohol, estrogens • Classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands • Urine: elevated uroporphyrinogen and pink fluorescence of urine under wood's lamp

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• Manage with chloroquine

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• Autosomal dominant • Defect in protoporphyrinogen oxidase

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• Photosensitive blistering rash • Abdominal and neurological symptoms • More common in south africans

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POEMS Syndrome: Polyneuropathy, Organomegaly, Endocrinopathy or Edema, M-protein and Skin abnormalities (including hyperpigmentation and hypertrichosis), also known as Crow–Fukase syndrome, Takatsuki disease. It is a rare syndrome, defined as the combination of a plasma-cell proliferative disorder (typically myeloma), polyneuropathy and organomegaly.

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Average age of onset is 50 years, ♂:♀ 2:1. Its 5 years survival is 60% if untreated

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Presentation: • Polyneuropathy: bilateral symmetric disturbance, involves both motor and sensory nerves, begins distally, and has a progressive proximal spread. No cranial or autonomic nerves involvement. Both demyelination and axonal degeneration are noted. • Organomegaly: liver, lymph nodes, and spleen are most frequently involved. • Multiple endocrinopathies, most patients have more than one endocrine abnormality. • POEMS syndrome is seen in the setting of a plasma cell dyscrasia. Although many plasma cell disorders have been reported in patients with POEMS syndrome, most patients are seen with osteosclerotic myeloma or monoclonal gammopathy of unknown significance (MGUS). Classic multiple myeloma has not been associated with the disease.

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Management: • No treatment was found, just correct the hematological abnormality • Conventional treatments for demyelinating neuropathy (Steroids, IV immunoglobulin and plasma exchange) are ineffective; treatment must be aimed at the hematological disorder.

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Systemic Mastocytosis results from a neoplastic proliferation of mast cells

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Features • Urticaria pigmentosa - produces a wheal on rubbing (Darier's sign) • Flushing • Abdominal pain • Monocytosis on the blood film

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Diagnosis • Raised serum tryptase levels • Urinary histamine

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• Patients with a hemoglobin of greater than 8 g/dl may travel without problems