Haem Flashcards

Question

A doctor suspects that their patient may be anaemic. The doctor orders a panel of blood tests. A FBC reveals a microcytic anaemia. The results of Iron Studies are below. Serum iron Low Total Iron Binding Capacity (TIBC) Elevated Ferritin Low C Reactive Protein 3 (NR 2-8) What is the cause of this patient's microcytic anaemia?

Answer 1

Iron Deficiency Anaemia

Answer 2

D Dimer D Dimer is a measure of fibrin degradation products and hence is a proxy measure of how much “clot” is being broken down by the body. It is not a very specific measure - it may be elevated for a large number of reasons that aren’t necessarily related to clotting. However, severely elevated levels (>1000) in the context of a patient with a clotting abnormality are suggestive of clot breakdown. Examples of conditions with elevated D dimers include PEs, DVTs and DIC.

Answer 3

Pancytopenia ``` To differentiate the commonest primary bone marrow failures on blood film, here is a helpful table: Fanconi anaemia Pancytopenia Most common Diamond-Blackfan anaemia Red cells only Shwachman-Diamond syndrome Neutropenia Dyskeratosis congenita Pancytopenia ```

Answer 4

Hodgkin's Lymphoma Hodgkin's Lymphoma (HL) [20% of lymphomas] Typically occurs in two groups of people - young adults and elderly patients. Men are disproportionately affected. A key precipitating factor is prior infection with Epstein Barr Virus (EBV). Malignant cells are predominantly mature B cells from a lymph node's germinal centre. It is staged using the Ann-Arbor system. Often, it is symptomless until the development of "B" symptoms - fever, drenching night sweats and weight loss. There will be asymmetrical lymphadenopathy, usually in the neck. Classically, there is lymph node pain after alcohol - though this is very rare. There is also the risk of developing SVC syndrome if left untreated. For diagnosis, clinical suspicion and CT-PET followed by lymph node biopsy is used. A blood film may show the presence of Reed-Sternberg cells. There are multiple subtypes of HL, the most common of which is the nodular sclerosing subtype (good prognosis).

Answer 5

Ibrutinib Chronic Lymphocyte Leukaemia (CLL) CLL is a slow lymphoproliferative disease, typically presenting in elderly men. Often asymptomatic and only detected incidentally on blood tests. Symptoms include Bone Marrow Failure (anaemia, thrombocytopenia and neutropenia) in the end stages, however typically the only symptoms will be generalised lymphadenopathy with weight loss, fever and night sweats. Richter's transformation may occur, where a low-grade CLL converts to a high grade, aggressive Diffuse Large B Cell Lymphoma. Blood tests will show a high WCC with elevated (mature) lymphocytes. A blood film may show smudge cells. Watchful waiting is usually the management of choice for early-moderate disease. Ibrutinib (a tyrosine kinase inhibitor) may be used for advanced or symptomatic cases.

Answer 6

Rouleaux Formation

Answer 7

Prothrombin Time Intrinsic and Extrinsic Pathways of the Clotting Cascade The clotting cascade fundamentally exists to turn a small action into a larger action. There are two main pathways - the intrinsic and extrinsic, which converge and join the common pathway. Fun fact: The “a” after clotting factors e.g. Xa stands for “activated”. The intrinsic pathway starts when the vascular endothelium is disrupted, exposing collagen. This exposed collagen then sets off a chain reaction resulting in factor X being converted to Xa. Intrinsic pathway = the injury pathway. The activity of this pathway is measured clinically using the APPT. The extrinsic pathway is much more sensitive. Heat, trauma, sepsi, chemicals and many other stimuli can begin this part of the clotting cascade. Extrinsic pathway = the “everything else” pathway. The activity of this pathway is measured clinically using the PT. Both pathways need calcium (factor IV) in order for clotting to occur. Both pathways then converge at the common pathway with the production of factor Xa from Factor X.

Answer 8

Epstein Barr Virus Hodgkin's Lymphoma (HL) [20% of lymphomas] Typically occurs in two groups of people - young adults and elderly patients. Men are disproportionately affected. A key precipitating factor is prior infection with Epstein Barr Virus (EBV). Malignant cells are predominantly mature B cells from a lymph node's germinal centre. It is staged using the Ann-Arbor system. Often, it is symptomless until the development of "B" symptoms - fever, drenching night sweats and weight loss. There will be asymmetrical lymphadenopathy, usually in the neck. Classically, there is lymph node pain after alcohol - though this is very rare. There is also the risk of developing SVC syndrome if left untreated. For diagnosis, clinical suspicion and CT-PET followed by lymph node biopsy is used. A blood film may show the presence of Reed-Sternberg cells. There are multiple subtypes of HL, the most common of which is the nodular sclerosing subtype (good prognosis).

Answer 9

Acute Myeloid Leukaemia Acute Myeloid Leukaemia (AML) AML typically affects two groups of people: adults (risk increases with age) and <2 year olds The typical presentation is of bone marrow failure - anaemia and thrombocytopenia - in combination with organ infiltration - hepatomegaly, gum infiltration or in severe cases into the CNS. There are multiple subtypes of AML. On a FBC, there will be a high white cell count with a preponderance of blast (immature) cells. A blood film may show the presence of neutrophils with auer rods. Treatment is mainly chemotherapy, though stem cell transplantation is an option. Symptomatic treatment with blood products is often also needed. Of note, the M3 subtype (acute promyelocytic leukaemia) can be treated specifically with all-trans retinoic acid.

Answer 10

Chronic Myeloid Leukaemia Chronic Myeloid Leukaemia (CML) CML is the overlap point between full blown leukaemias and the other myeloproliferative diseases. The median age of diagnosis is around 50 years old. Often, CML is diagnosed incidentally. Classically it causes massive splenomegaly due to splenic infiltration of myeloid cells. A white cell count will show an elevated neutrophil count. If CML is suspected, genetic testing for the philadelphia chromosome (9;22 translocation) or the BCR-ABL fusion gene should be performed. A rationally designed small molecule inhibitor, imatinib (when BCR-ABL is present) can induce remission in nearly every case in the chronic phase of the disease.

Answer 11

Dyskeratosis Congenita Dyskeratosis congenita is an inherited bone marrow failure which typically presents around age 15. The classical triad is of nail dystrophy (nail loss, longitudinal ridging), oral leukoplakia (white patches in the mouth) and skin pigmentation (lace like hyperpigmentation of skin creases), although this is thought to occur less commonly than previously described. A newer definition involves at least one of the features of the classical triad, with associated bone marrow failure (aplastic anaemia) and two other internal signs (like pulmonary fibrosis). The condition is caused by mutations in genes which protect telomeres. Telomeres protect the ends of chromosomes from damage and are associated with aging. Essentially, this condition reflects abnormal, advanced, cellular aging.

Answer 12

Shwachman Diamond syndrome Shwachman-Diamond syndrome is an inherited, autosomal recessive condition characterised by neutropenia and other classical features. Generally, there is pancreatic dysfunction - resulting in fatty stools and hepatic impairment. They also have a very short stature, with most patients being less than the fifth percentile for height and a preponderance of skeletal issues. It is typically diagnosed in childhood and is the second most common cause of pancreatic exocrine dysfunction in children - other than cystic fibrosis. It arises because the SBDS gene is important for ribosomal function. How this causes the phenotype seen in Shwachman-Diamond syndrome is unclear. This syndrome is different to Diamond–Blackfan syndrome, which typically affects red blood cells only and has a different clinical presentation.

Answer 13

Reed-Sternberg cells

Answer 14

Glucose-6-phosphate dehydrogenase deficiency Absolute levels of G6PD may be normal during an acute haemolytic crisis - to reflect an increase in RBC formation. However, the actual amount of G6PD per erythrocyte is low. Mode of inheritance is X linked recessive. Please note - there is such a thing as X linked dominant! You must be specific that it is X linked recessive.

Answer 15

Rouleaux formation

Answer 16

Autosomal recessive

Answer 17

X linked recessive Absolute levels of G6PD may be normal during an acute haemolytic crisis - to reflect an increase in RBC formation. However, the actual amount of G6PD per erythrocyte is low. Mode of inheritance is X linked recessive. Please note - there is such a thing as X linked dominant! You must be specific that it is X linked recessive.

Answer 18

Gluten avoidance

Answer 19

Shwachman Diamond syndrome Shwachman-Diamond syndrome is an inherited, autosomal recessive condition characterised by neutropenia and other classical features. Generally, there is pancreatic dysfunction - resulting in fatty stools and hepatic impairment. They also have a very short stature, with most patients being less than the fifth percentile for height and a preponderance of skeletal issues. It is typically diagnosed in childhood and is the second most common cause of pancreatic exocrine dysfunction in children - other than cystic fibrosis. It arises because the SBDS gene is important for ribosomal function. How this causes the phenotype seen in Shwachman-Diamond syndrome is unclear. This syndrome is different to Diamond–Blackfan syndrome, which typically affects red blood cells only and has a different clinical presentation.

Answer 20

Chronic Myeloid Leukaemia Chronic Myeloid Leukaemia (CML) CML is the overlap point between full blown leukaemias and the other myeloproliferative diseases. The median age of diagnosis is around 50 years old. Often, CML is diagnosed incidentally. Classically it causes massive splenomegaly due to splenic infiltration of myeloid cells. A white cell count will show an elevated neutrophil count. If CML is suspected, genetic testing for the philadelphia chromosome (9;22 translocation) or the BCR-ABL fusion gene should be performed. A rationally designed small molecule inhibitor, imatinib (when BCR-ABL is present) can induce remission in nearly every case in the chronic phase of the disease.

Answer 21

Activated Partial Thromboplastin Time Intrinsic and Extrinsic Pathways of the Clotting Cascade The clotting cascade fundamentally exists to turn a small action into a larger action. There are two main pathways - the intrinsic and extrinsic, which converge and join the common pathway. Fun fact: The “a” after clotting factors e.g. Xa stands for “activated”. The intrinsic pathway starts when the vascular endothelium is disrupted, exposing collagen. This exposed collagen then sets off a chain reaction resulting in factor X being converted to Xa. Intrinsic pathway = the injury pathway. The activity of this pathway is measured clinically using the APPT. The extrinsic pathway is much more sensitive. Heat, trauma, sepsi, chemicals and many other stimuli can begin this part of the clotting cascade. Extrinsic pathway = the “everything else” pathway. The activity of this pathway is measured clinically using the PT. Both pathways need calcium (factor IV) in order for clotting to occur. Both pathways then converge at the common pathway with the production of factor Xa from Factor X.

Answer 22

Iron Deficiency Anaemia

Answer 23

Acute Myeloid Leukaemia Fanconi anaemia is the most common type of inherited primary bone marrow failure. It presents between the ages of 5-9 with skeletal abnormalities (abnormal thumbs), short stature, cafe au lait spots and pancytopenia. The disease is due to dysfunctioning DNA repair genes such as FANCA. There is a high risk of developing acute myeloid leukaemia, approximately 10% of patients diagnosed with fanconi anaemia will develop this. 30% will develop some myelodysplastic syndrome. Please note this is different to Fanconi syndrome, which is a renal disease

Answer 24

Auer rods Acute Myeloid Leukaemia (AML) AML typically affects two groups of people: adults (risk increases with age) and <2 year olds The typical presentation is of bone marrow failure - anaemia and thrombocytopenia - in combination with organ infiltration - hepatomegaly, gum infiltration or in severe cases into the CNS. There are multiple subtypes of AML. On a FBC, there will be a high white cell count with a preponderance of blast (immature) cells. A blood film may show the presence of neutrophils with auer rods. Treatment is mainly chemotherapy, though stem cell transplantation is an option. Symptomatic treatment with blood products is often also needed. Of note, the M3 subtype (acute promyelocytic leukaemia) can be treated specifically with all-trans retinoic acid.

Answer 25

Erythropoietin

Answer 26

Neutropenia ``` To differentiate the commonest primary bone marrow failures on blood film, here is a helpful table: Fanconi anaemia Pancytopenia Most common Diamond-Blackfan anaemia Red cells only Shwachman-Diamond syndrome Neutropenia Dyskeratosis congenita Pancytopenia ```

Answer 27

Reticulocyte count Reticulocytes are immature red blood cells which still have residual ribosomes. Ribosomes are basophilic and hence stain darkly. The number of reticulocytes in peripheral circulation approximately reflects the status of erythropoiesis - the more erythropoiesis, the more reticulocytes. Automated white cell counts in hospitals can be confused by reticulocytes. Automated white cell counts are not (always) accurate in the presence of e.g. severe haemolytic anaemia. The automated white cell count will read reticulocytes as neutrophils. A manual differentiation (a haematologist reviewing under the microscope) or reticulocyte count can be ordered to identify the level of reticulocytosis.

Answer 28

Bone Marrow Biopsy

Answer 29

Factor X Intrinsic and Extrinsic Pathways of the Clotting Cascade The clotting cascade fundamentally exists to turn a small action into a larger action. There are two main pathways - the intrinsic and extrinsic, which converge and join the common pathway. Fun fact: The “a” after clotting factors e.g. Xa stands for “activated”. The intrinsic pathway starts when the vascular endothelium is disrupted, exposing collagen. This exposed collagen then sets off a chain reaction resulting in factor X being converted to Xa. Intrinsic pathway = the injury pathway. The activity of this pathway is measured clinically using the APPT. The extrinsic pathway is much more sensitive. Heat, trauma, sepsi, chemicals and many other stimuli can begin this part of the clotting cascade. Extrinsic pathway = the “everything else” pathway. The activity of this pathway is measured clinically using the PT. Both pathways need calcium (factor IV) in order for clotting to occur. Both pathways then converge at the common pathway with the production of factor Xa from Factor X.

Answer 30

Vitamin K epoxide Vitamin K dependent clotting factors The vitamin K dependent clotting factors are factors 2, 7, 9 and 10. In addition, the anticoagulants protein C and S also rely on vitamin K. Warfarin inhibits the enzyme Vitamin K epoxide and prevents recycling of vitamin K - leading to a net reduction in levels of vitamin K dependent clotting factors. If initiating warfarin treatment, for the first few days there is a PRO-coagulant effect. This is due to the different half lifes of the anticoagulants protein C + S relative to the clotting factors. Protein C and S have a shorter half life, so these anticoagulant proteins disappear - leaving normal levels of the other clotting factors. This means there is a net procoagulant effect. Typically, people are bridged with low molecular weight heparin for the first few days of warfarin treatment.

Answer 31

Multiple Myeloma Multiple Myeloma is a malignancy of plasma cells. It is differentiated from the related conditions MGUS and Smouldering Myeloma by the presence of end organ damage, the so called "CRAB" symptoms. Calcium (elevated), Renal failure, Anaemia and Bone lesions. MGUS has <10% plasma cells in the bone marrow on biopsy, where as SM and multiple myeloma have >10%. Most commonly, the plasma cells will produce large amount of defective immunoglobulins - mostly IgG (less commonly IgA). These may be detected by serum electrophoresis - producing a graph of the molecular weights of proteins in the blood. There will be a large, single, spike. Urinary bence jones proteins are also used in the diagnosis of MM - these are the light chains of immunoglobulins which may be secreted in urine - but not always. Other diagnostic factors include: an elevated ESR and rouleaux formation on a blood film (both due to the increased protein [immunoglobulin] concentration in the blood).

Answer 32

Von Willebrand's Disease Von Willebrand's Disease Von Willebrand’s disease is a disorder of platelet function caused by a reduction in function or number of Von Willebrand Factor (vWF). Normally, vWF is responsible for binding to other proteins, notably factor VIII, collagen and platelets directly. By binding these three things together, it stabilises the platelet plug and increases the strength of the initial platelet plug in primary haemostasis. Factor VIII is normally bound to vWF in circulation. If vWF is not present, then Factor VIII is rapidly degraded. Hence, Von Willebrand’s disease will also decrease the function of the intrinsic clotting pathway due to reduced levels of Factor VIII. Most Von Willebrand’s disease is mild and many people do not realise they have it. If they are symptomatic, then usually it will present as easy bruising and nosebleeds. Women may experience heavy periods. Blood tests will reveal a prolonged bleeding time (as this measures platelet function directly) and a prolonged APTT (due to increased degradation of Factor VIII). Platelet count, PT and INR will be normal. Haemophillia does not affect the bleeding time Levels of vWF may be normal OR low - depending if the issue is with the function of vWF or if the issue is with a lack of production of vWF

Answer 33

Pernicious Anaemia

Answer 34

Factor VIII Von Willebrand's Disease Von Willebrand’s disease is a disorder of platelet function caused by a reduction in function or number of Von Willebrand Factor (vWF). Normally, vWF is responsible for binding to other proteins, notably factor VIII, collagen and platelets directly. By binding these three things together, it stabilises the platelet plug and increases the strength of the initial platelet plug in primary haemostasis. Factor VIII is normally bound to vWF in circulation. If vWF is not present, then Factor VIII is rapidly degraded. Hence, Von Willebrand’s disease will also decrease the function of the intrinsic clotting pathway due to reduced levels of Factor VIII. Most Von Willebrand’s disease is mild and many people do not realise they have it. If they are symptomatic, then usually it will present as easy bruising and nosebleeds. Women may experience heavy periods. Blood tests will reveal a prolonged bleeding time (as this measures platelet function directly) and a prolonged APTT (due to increased degradation of Factor VIII). Platelet count, PT and INR will be normal. Haemophillia does not affect the bleeding time Levels of vWF may be normal OR low - depending if the issue is with the function of vWF or if the issue is with a lack of production of vWF

Answer 35

Acute myeloid leukaemia

Answer 36

Metallic heart valve

Answer 37

Haemolytic anaemia

Answer 38

Essential thrombocytosis

Answer 39

Plasma cells

Answer 40

Haemophilia A Haemophilias Haemophillias are a collection of inherited, X-linked recessive disorders of clotting factors. There are two main types: Haemophilia A - a deficiency in clotting factor VIII Haemophilia B (aka Christmas disease) - a deficiency in clotting factor IX Diagnosis can be made on the basis of abnormal, spontaneous or prolonged bleeding that is often identified in childhood. Bleeding into joints (haemarthrosis) or muscles is common. A common presentation is prolonged bleeding after dental surgery. If requested, blood tests will show an increased APTT (reflecting decreased activity of the intrinsic pathway, which factors VIII and IX are involved in), normal PT and decreased levels of whichever clotting factor is affected. The bleeding time is typically normal - the issue here isn't the initial platelet plug as in primary haemostasis (which does not rely on clotting factors) but rather coagulation, which is part of secondary haemostasis and is responsible for a more permanent, fibrin cross-linked clot.

Answer 41

X linked recessive Haemophilias Haemophillias are a collection of inherited, X-linked recessive disorders of clotting factors. There are two main types: Haemophilia A - a deficiency in clotting factor VIII Haemophilia B (aka Christmas disease) - a deficiency in clotting factor IX Diagnosis can be made on the basis of abnormal, spontaneous or prolonged bleeding that is often identified in childhood. Bleeding into joints (haemarthrosis) or muscles is common. A common presentation is prolonged bleeding after dental surgery. If requested, blood tests will show an increased APTT (reflecting decreased activity of the intrinsic pathway, which factors VIII and IX are involved in), normal PT and decreased levels of whichever clotting factor is affected. The bleeding time is typically normal - the issue here isn't the initial platelet plug as in primary haemostasis (which does not rely on clotting factors) but rather coagulation, which is part of secondary haemostasis and is responsible for a more permanent, fibrin cross-linked clot.

Answer 42

Chronic Lymphocytic Leukaemia Chronic Lymphocyte Leukaemia (CLL) CLL is a slow lymphoproliferative disease, typically presenting in elderly men. Often asymptomatic and only detected incidentally on blood tests. Symptoms include Bone Marrow Failure (anaemia, thrombocytopenia and neutropenia) in the end stages, however typically the only symptoms will be generalised lymphadenopathy with weight loss, fever and night sweats. Richter's transformation may occur, where a low-grade CLL converts to a high grade, aggressive Diffuse Large B Cell Lymphoma. Blood tests will show a high WCC with elevated (mature) lymphocytes. A blood film may show smudge cells. Watchful waiting is usually the management of choice for early-moderate disease. Ibrutinib (a tyrosine kinase inhibitor) may be used for advanced or symptomatic cases.

Answer 43

Anaemia of chronic disease

Answer 44

Anaemia Diamond-Blackfan anaemia is a congenital disorder affecting haematological stem cells. Typically, only red blood cells are affected rather than other blood cell lineages. Symptoms are usually detected in infancy and diagnosis is made off the results of blood tests (showing anaemia, low reticulocytes and elevated fetal haemoglobin). A bone marrow biopsy would also reveal decreased erythroid precursors. Other features which may be present include craniofacial malformations, such as cleft palate or cardiac defects. Please note, this syndrome is different from Shwachman-Diamond syndrome, which predominantly affects neutrophils.

Answer 45

Phlebotomy

Answer 46

Acute Myeloid leukaemia Acute Myeloid Leukaemia (AML) AML typically affects two groups of people: adults (risk increases with age) and <2 year olds The typical presentation is of bone marrow failure - anaemia and thrombocytopenia - in combination with organ infiltration - hepatomegaly, gum infiltration or in severe cases into the CNS. There are multiple subtypes of AML. On a FBC, there will be a high white cell count with a preponderance of blast (immature) cells. A blood film may show the presence of neutrophils with auer rods. Treatment is mainly chemotherapy, though stem cell transplantation is an option. Symptomatic treatment with blood products is often also needed. Of note, the M3 subtype (acute promyelocytic leukaemia) can be treated specifically with all-trans retinoic acid.

Answer 47

Beta Globin

Answer 48

Autosomal dominant

Answer 49

Autosomal dominant

Answer 50

Multiple Myeloma Multiple Myeloma is a malignancy of plasma cells. It is differentiated from the related conditions MGUS and Smouldering Myeloma by the presence of end organ damage, the so called "CRAB" symptoms. Calcium (elevated), Renal failure, Anaemia and Bone lesions. MGUS has <10% plasma cells in the bone marrow on biopsy, where as SM and multiple myeloma have >10%. Most commonly, the plasma cells will produce large amount of defective immunoglobulins - mostly IgG (less commonly IgA). These may be detected by serum electrophoresis - producing a graph of the molecular weights of proteins in the blood. There will be a large, single, spike. Urinary bence jones proteins are also used in the diagnosis of MM - these are the light chains of immunoglobulins which may be secreted in urine - but not always. Other diagnostic factors include: an elevated ESR and rouleaux formation on a blood film (both due to the increased protein [immunoglobulin] concentration in the blood).

Answer 51

Disseminated Intravascular Coagulation Disseminated Intravascular Coagulation Disseminated Intravascular Coagulation is a rare, catastrophic clotting event. It is characterised by simultaneous, widespread clotting throughout the body which rapidly uses up clotting factors and fibrin. When all the clotting factors, fibrin, platelets etc are consumed, uncontrollable bleeding can occur. This typically occurs in the context of severe, systemic injury such as widespread trauma, obstetric haemorrhage, malignancy or sepsis. It has a very high mortality rate. Blood tests would show elevated INR, APTT, Thrombin Time, D Dimer and Bleeding time. There would be a decrease in platelet count, fibrinogen and clotting factor levels.

Answer 52

Calcium Intrinsic and Extrinsic Pathways of the Clotting Cascade The clotting cascade fundamentally exists to turn a small action into a larger action. There are two main pathways - the intrinsic and extrinsic, which converge and join the common pathway. Fun fact: The “a” after clotting factors e.g. Xa stands for “activated”. The intrinsic pathway starts when the vascular endothelium is disrupted, exposing collagen. This exposed collagen then sets off a chain reaction resulting in factor X being converted to Xa. Intrinsic pathway = the injury pathway. The activity of this pathway is measured clinically using the APPT. The extrinsic pathway is much more sensitive. Heat, trauma, sepsi, chemicals and many other stimuli can begin this part of the clotting cascade. Extrinsic pathway = the “everything else” pathway. The activity of this pathway is measured clinically using the PT. Both pathways need calcium (factor IV) in order for clotting to occur. Both pathways then converge at the common pathway with the production of factor Xa from Factor X.

Answer 53

Ann-Arbor staging Hodgkin's Lymphoma (HL) [20% of lymphomas] Typically occurs in two groups of people - young adults and elderly patients. Men are disproportionately affected. A key precipitating factor is prior infection with Epstein Barr Virus (EBV). Malignant cells are predominantly mature B cells from a lymph node's germinal centre. It is staged using the Ann-Arbor system. Often, it is symptomless until the development of "B" symptoms - fever, drenching night sweats and weight loss. There will be asymmetrical lymphadenopathy, usually in the neck. Classically, there is lymph node pain after alcohol - though this is very rare. There is also the risk of developing SVC syndrome if left untreated. For diagnosis, clinical suspicion and CT-PET followed by lymph node biopsy is used. A blood film may show the presence of Reed-Sternberg cells. There are multiple subtypes of HL, the most common of which is the nodular sclerosing subtype (good prognosis).

Answer 54

All Trans Retinoic Acid Acute Myeloid Leukaemia (AML) AML typically affects two groups of people: adults (risk increases with age) and <2 year olds The typical presentation is of bone marrow failure - anaemia and thrombocytopenia - in combination with organ infiltration - hepatomegaly, gum infiltration or in severe cases into the CNS. There are multiple subtypes of AML. On a FBC, there will be a high white cell count with a preponderance of blast (immature) cells. A blood film may show the presence of neutrophils with auer rods. Treatment is mainly chemotherapy, though stem cell transplantation is an option. Symptomatic treatment with blood products is often also needed. Of note, the M3 subtype (acute promyelocytic leukaemia) can be treated specifically with all-trans retinoic acid.

Answer 55

Haptoglobin

Answer 56

IgG Multiple Myeloma is a malignancy of plasma cells. It is differentiated from the related conditions MGUS and Smouldering Myeloma by the presence of end organ damage, the so called "CRAB" symptoms. Calcium (elevated), Renal failure, Anaemia and Bone lesions. MGUS has <10% plasma cells in the bone marrow on biopsy, where as SM and multiple myeloma have >10%. Most commonly, the plasma cells will produce large amount of defective immunoglobulins - mostly IgG (less commonly IgA). These may be detected by serum electrophoresis - producing a graph of the molecular weights of proteins in the blood. There will be a large, single, spike. Urinary bence jones proteins are also used in the diagnosis of MM - these are the light chains of immunoglobulins which may be secreted in urine - but not always. Other diagnostic factors include: an elevated ESR and rouleaux formation on a blood film (both due to the increased protein [immunoglobulin] concentration in the blood).

Answer 57

Richter's Transformation Chronic Lymphocyte Leukaemia (CLL) CLL is a slow lymphoproliferative disease, typically presenting in elderly men. Often asymptomatic and only detected incidentally on blood tests. Symptoms include Bone Marrow Failure (anaemia, thrombocytopenia and neutropenia) in the end stages, however typically the only symptoms will be generalised lymphadenopathy with weight loss, fever and night sweats. Richter's transformation may occur, where a low-grade CLL converts to a high grade, aggressive Diffuse Large B Cell Lymphoma. Blood tests will show a high WCC with elevated (mature) lymphocytes. A blood film may show smudge cells. Watchful waiting is usually the management of choice for early-moderate disease. Ibrutinib (a tyrosine kinase inhibitor) may be used for advanced or symptomatic cases.

Answer 58

Activated partial thromboplastin time Heparin works by increasing the action of antithrombin III. Antithrombin III inactivates thrombin and factors IX, X and XI. There are two main types in clinical practice - low molecular weight heparin - LMWH- (does not require monitoring) and unfractionated heparin (requires APTT monitoring). Heparins predominantly affects the intrinsic pathway of clotting. Heparins In severe bleeding an antidote, protamine sulfate, may be given. It doesn't completely reverse LMWH, however.

Answer 59

Reticulocyte

Answer 60

APTT Haemophilias Haemophillias are a collection of inherited, X-linked recessive disorders of clotting factors. There are two main types: Haemophilia A - a deficiency in clotting factor VIII Haemophilia B (aka Christmas disease) - a deficiency in clotting factor IX Diagnosis can be made on the basis of abnormal, spontaneous or prolonged bleeding that is often identified in childhood. Bleeding into joints (haemarthrosis) or muscles is common. A common presentation is prolonged bleeding after dental surgery. If requested, blood tests will show an increased APTT (reflecting decreased activity of the intrinsic pathway, which factors VIII and IX are involved in), normal PT and decreased levels of whichever clotting factor is affected. The bleeding time is typically normal - the issue here isn't the initial platelet plug as in primary haemostasis (which does not rely on clotting factors) but rather coagulation, which is part of secondary haemostasis and is responsible for a more permanent, fibrin cross-linked clot.