Haematology

Question 1

Hypersensitivity Reactions

Answer 1

Type 1( Allergic Reactions)
-Hay Fever
-Eczema
-Contact Dermatitis
-Asthma
-Anaphylaxis

Type 2( Antibody-dependent cytotoxic reactions)
-Drug-induced hemolytic anemia
- Acute transfusion reactions
- Goodpasture syndrome

Question 2

Hypersensitivity Reactions

Answer 2

Type 3( Immune complex-mediated reactions)
-SLE
- Poststreptococcal glomerulonephritis

Type 4 ( Cell mediated delayed reactions)
-Contact Dermatitis
-BCG immunization

Question 3

Von Willebrand Disease

Answer 3

• Deficiency of Von Willebrand factor.
  -3 types.
  -vWF is a protein made in endothelial cells and megakaryocytes.
  -Nose bleeding, Menorrhagia, Joint bleeding, Recurrent GI bleeding.
  -Rx is VWF, Factor 8 and Desmopressin (DDAVP).

Question 5

Aplastic crisis in Heredatry spherocytisis or sickle cell Anemia

Answer 5

Parvovirus B19

Question 6

CLL

Answer 6

Administering intravenous immunoglobulin (IVIg) therapy is recommended for patients with chronic lymphocytic leukaemia (CLL) who have severe hypogammaglobulinemia and recurrent bacterial infections despite prophylactic antibiotics.

Question 7

Primary polycythemia Ix

Answer 7

Molecular studies for JAK2, MPL and CALR mutation.

Question 8

Aplastic Crisis

Answer 8

Aplastic crisis in sickle cell anaemia (SSA) is caused by infection with the parvovirus B19.

Question 9

Coagulopathy

Answer 9

To correct a coagulopathy you need to aim for:

Fibrinogen >1.0 g/L
Platelets >50 ×109/L
PT and APTT <1.5 upper range of normal

Question 10

CLL

Answer 10

Immunophenotyping of white Cells

Question 11

Hemochromatosis

Answer 11

• Autosomal Recessive
• It is caused by the inheritance of mutations in the HFE gene on both copies of chromosome 6.

SCREENING
- Transferrin saturation and Ferritin
- Genetic testing for HFE mutation

• transferrin saturation > 55% in men or > 50% in women
• raised ferritin (e.g. > 500 ug/l) and iron
• low TIBC

Question 12

Haptoglobin

Answer 12

Low haptoglobin levels are found in haemolytic anaemias

Question 13

Intravascular and Extravascular Haemolysis

Answer 13

Intravascular haemolysis: causes
- mismatched blood transfusion
- G6PD deficiency*
- red cell fragmentation: heart valves, TTP, DIC, HUS
- Paroxysmal nocturnal haemoglobinuria
- Cold autoimmune haemolytic anaemia

Extravascular haemolysis: causes
- haemoglobinopathies: sickle cell, thalassaemia
- hereditary spherocytosis
- Haemolytic disease of newborn
- Warm autoimmune haemolytic anaemia

Question 14

Difference between Leukaemoid reaction and CML

Answer 14

Leukaemoid reaction
- high leucocyte alkaline phosphatase score
- toxic granulation (Dohle bodies) in the white cells
- ‘left shift’ of neutrophils i.e. three or fewer segments of the nucleus

Chronic myeloid leukaemia
low leucocyte alkaline phosphatase score

Question 15

TTP

Answer 15

in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor.
TTP presents with a pentad of fever, neuro signs, thrombocytopenia, haemolytic anaemia and renal failure

Question 16

Polycythemia Rubra Vera

Answer 16

Polycythaemia rubra vera - JAK2 mutation

Question 17

VTE

Answer 17

Venous thromoboembolism - length of anticoagulation
provoked (e.g. recent surgery): 3 months
unprovoked: 6 months

Question 18

Neutropenia

Answer 18

Mild 1.0 - 1.5
Moderate 0.5 - 1.0
Severe < 0.5

Causes
viral
- HIV
- Epstein-Barr virus
- hepatitis
drugs
- cytotoxics
- carbimazole
- clozapine
- benign ethnic neutropaenia
common in people of black African and Afro-Caribbean ethnicity
requires no treatment
Haematological malignancy
- myelodysplastic malignancies
- aplastic anemia
rheumatological conditions
systemic lupus erythematosus: mechanisms include circulating antineutrophil antibodies
rheumatoid arthritis: e.g. hypersplenism as in Felty’s syndrome
severe sepsis
haemodialysis

Question 19

Factor V Leiden

Answer 19

Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.

It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal.

Question 20

Haematological malignancies: infections

Answer 20

Viruses
EBV: Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
HTLV-1: Adult T-cell leukaemia/lymphoma
HIV-1: High-grade B-cell lymphoma

Bacteria
Helicobacter pylori: gastric lymphoma (MALT)

Protozoa
Malaria: Burkitt’s lymphoma

Question 21

CLL

Answer 21

CLL - immunophenotyping is investigation of choice

Question 23

Platelet transfusions

Answer 23

Platelet transfusions are at particular risk of bacterial contamination as they are stored at room temperature

Question 24

Acute haemolytic transfusion reaction.

Answer 24

Acute haemolytic transfusion reaction results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. This is usually the result of red blood cell destruction by IgM-type antibodies.

Question 25

Non-haemolytic febrile reaction

Answer 25

Febrile reactions due to white blood cell HLA antibodies

Question 26

Difference between Waldenstrom macroglobulinemia and multiple myeloma

Answer 26

Waldenstrom's macroglobulinaemia - Organomegaly with no bone lesions Multiple myeloma - Bone lesions with no organomegaly

Question 27

Polycythaemia vera: Management

Answer 27

Polycythaemia vera is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has a peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly. Management aspirin reduces the risk of thrombotic events venesection first-line treatment to keep the haemoglobin in the normal range chemotherapy hydroxyurea - slight increased risk of secondary leukaemia phosphorus-32 therapy Prognosis thrombotic events are a significant cause of morbidity and mortality 5-15% of patients progress to myelofibrosis 5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)

Question 28

ITP

Answer 28

Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex Investigations - antiplatelet autoantibodies (usually IgG) - bone marrow aspiration shows megakaryocytes in the marrow.

Question 29

Factor V Leiden mutation

Answer 29

Factor V Leiden mutation results in activated protein C resistance

Question 30

HIT

Answer 30

Heparin-induced thrombocytopaenia - antibodies form against complexes of platelet factor 4 (PF4) and heparin

Question 31

Sideroblastic Anemia

Answer 31

Congenital cause: delta-aminolevulinate synthase-2 deficiency Acquired causes myelodysplasia alcohol lead anti-TB medications Investigations full blood count hypochromic microcytic anaemia (more so in congenital) iron studies high ferritin high iron high transferrin saturation blood film basophilic stippling of red blood cells bone marrow Prussian blue staining will show ringed sideroblasts Management supportive treat any underlying cause pyridoxine may help

Question 32

Polycythemia rubra Vera

Answer 32

Polycythaemia rubra vera - around 5-15% progress to myelofibrosis or AML

Question 35

Essential Thrombocytosis

Answer 35

Essential thrombocytosis is one of the myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis. Megakaryocyte proliferation results in an overproduction of platelets. Features platelet count > 600 * 109/l both thrombosis (venous or arterial) and haemorrhage can be seen a characteristic symptom is a burning sensation in the hands a JAK2 mutation is found in around 50% of patients Management - hydroxyurea (hydroxycarbamide) - interferon-α is also used in younger patients - low-dose aspirin may be used to reduce the thrombotic risk

Question 36

TTP

Answer 36

Abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels in TTP, there is a deficiency of protease which breakdowns large multimers of von Willebrand's factor overlaps with haemolytic uraemic syndrome (HUS) Management - No antibiotics - may worsen outcome - Plasma exchange is the treatment of choice - Steroids, immunosuppressants vincristine

Question 37

Hydroxycarbamide

Answer 37

Sickle cell patients should be started on long term hydroxycarbamide to reduce the incidence of complications and acute crises

Question 38

Acute Myeloid Leukemia

Answer 38

Poor prognostic features > 60 years > 20% blasts after first course of chemo cytogenetics: deletions of chromosome 5 or 7 Acute promyelocytic leukaemia M3 associated with t(15;17) fusion of PML and RAR-alpha genes presents younger than other types of AML (average = 25 years old) Auer rods (seen with myeloperoxidase stain) DIC or thrombocytopenia often at presentation good prognosis

Question 39

EMA Binding test

Answer 39

The EMA binding test should be used to diagnose hereditary spherocytosis - the osmotic fragility test is no longer widely used

Question 40

CLL

Answer 40

Investigations - full blood count: - lymphocytosis - Anaemia: may occur either due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA) - Thrombocytopenia: may occur either due to bone marrow replacement or immune thrombocytopenia (ITP) - blood film: smudge cells (also known as smear cells) - Immunophenotyping is the key investigation

Question 41

Myelofibrosis

Answer 41

Myelofibrosis - most common presenting symptom - lethargy. - Thought to be caused by hyperplasia of abnormal megakaryocytes. - anaemia - 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

Question 42

ITP

Answer 42

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. -first-line treatment for ITP is oral prednisolone pooled normal human immunoglobulin (IVIG) may also be used. -Evan's syndrome ITP in association with autoimmune haemolytic anaemia (AIHA)

Question 43

Aplastic Crisis

Answer 43

The sudden fall in haemoglobin without an appropriate reticulocytosis (3% is just above the normal range) is typical of an aplastic crisis, usually secondary to parvovirus infection

Question 44

Multiple Myeloma

Answer 44

CRAB features of multiple myeloma = hypercalcaemia, Renal failure, Anaemia (and thrombocytopenia), and Bone fractures/lytic lesions

Question 45

Multiple Myeloma

Answer 45

Protein electrophoresis raised concentrations of monoclonal IgA/IgG proteins will be present in the serum in the urine, they are known as Bence Jones proteins Bone marrow aspiration confirms the diagnosis if the number of plasma cells is significantly raised Imaging historically a skeletal survey has been done to look for bone lesions however, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull' Diagnostic criteria The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma. Major criteria Plasmacytoma (as demonstrated on evaluation of biopsy specimen) 30% plasma cells in a bone marrow sample Elevated levels of M protein in the blood or urine

Question 46

Von Willebrand’s disease

Answer 46

Von Willebrand's disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion. - Management tranexamic acid for mild bleeding desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells factor VIII concentrate

Question 47

LAP

Answer 47

Raised in myelofibrosis leukaemoid reactions polycythaemia rubra vera infections steroids, Cushing's syndrome pregnancy, oral contraceptive pill Low in chronic myeloid leukaemia pernicious anaemia paroxysmal nocturnal haemoglobinuria infectious mononucleosis

Question 49

Acute promyelocytic leukaemia

Answer 49

APML is associated with the t(15;17) translocation which causes fusion of the PML and RAR-alpha genes. Features presents younger than other types of AML (average = 25 years old) DIC or thrombocytopenia often at presentation good prognosis APML is treated with all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemotherapy.

Question 50

SCA

Answer 50

Sickle cell patients should be started on long term hydroxycarbamide to reduce the incidence of complications and acute crises

Question 51

ALL

Answer 51

Good prognostic factors French-American-British (FAB) L1 type common ALL pre-B phenotype low initial WBC del(9p) Poor prognostic factors FAB L3 type T or B cell surface markers Philadelphia translocation, t(9;22) age < 2 years or > 10 years male sex CNS involvement high initial WBC (e.g. > 100 * 109/l) non-Caucasian

Question 52

Von Willebrand's disease

Answer 52

Desmopressin is used in the management of Von Willebrand's disease

Question 53

Increase Ferritin Levels

Answer 53

Inflammation (due to ferritin being an acute phase reactant) Alcohol excess Liver disease Chronic kidney disease Malignancy Primary iron overload (hereditary haemochromatosis) Secondary iron overload (e.g. following repeated transfusion

Question 54

Alpha-thalassaemia

Answer 54

Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin Overview 2 separate alpha-globulin genes are located on each chromosome 16 Clinical severity depends on the number of alpha globulin alleles affected: If 1 or 2 alpha globulin alleles are affected then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal If are 3 alpha globulin alleles are affected results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)