Anaemia And Cancers Flashcards
1
Q
What is anaemia characterized by?
A
Reduction in Hb and Haematocrit levels
The type of anaemia is indicated by MCV.
2
Q
What does Haematocrit measure?
A
The ratio of RBC to the volume of blood.
3
Q
What does MCV stand for and what does it represent?
A
Mean Corpuscular Volume; it represents the average size of red blood cells and used to indicate the type of anaemia.
4
Q
What is TIBC?
A
TIBC is total iron binding capacity, indicating how much ferritin is bound to iron.
5
Q
What is RDW?
A
RDW is the red cell density width to indicate the variety of RBCs and their size and volume. A high RDW indicates large variety in the RBCs size and volume, between the smallest RBC and the largest RBC.
6
Q
What is the normal range of haemoglobin for women?
A
120-160 g/dL
7
Q
What is the normal range of haemoglobin for men?
A
135-175 g/dL
8
Q
Which enzyme catalyzes the conversion of DHF to THF?
A
DHF reductase
9
Q
What are the common causes of folate deficiency?
A
- Inhibition of DHF reductase by methotrexate and trimethoprim
- Inhibition of thymidylate synthase by 5-fluorouracil
- Decreased intake
- Malabsorption due to coeliac disease, alcohol abuse
- Dialysis causes folate malabsorption
- Increased utilization from pregnancy, lactation, malignancy, and haemolytic anaemia
10
Q
What is the relationship between Vitamin B12 deficiency and pernicious anaemia?
A
Vitamin B12 deficiency is associated with autoantibodies directed to the parietal cells, causing gastritis and an increase in serum gastrin.
11
Q
What characterizes microcytic anaemia?
A
Low MCV and Hb.
12
Q
What are the most common causes of microcytic anaemia?
A
- Lead poisoning
- Iron deficiency
- Thalassemia
- Sideroblastic anaemia
13
Q
What is the primary cause of iron deficiency anaemia?
A
- Dietary insufficient intake, such as greater demand in pregnancy
- Malabsorption due to coeliac’s or post-gastric surgery
- Blood loss from colon polyps, hookworm disease GI bleeding or intravascular haemolytic anaemia.
14
Q
What clinical signs are associated with iron deficiency anaemia?
A
- Restless leg syndrome
- Koilonychia
- Pallor
- Pagophagia (compulsion to eat ice)
15
Q
What does RDW indicate in the context of anaemia?
A
Red cell density width; a high RDW indicates a large variety in RBC size and volume.
16
Q
What distinguishes iron deficiency anaemia from anaemia of chronic disease?
A
Soluble transferrin ferritin assay; STFR is raised in iron deficiency.
17
Q
What is the primary mechanism behind anaemia of chronic disease?
A
Host defence theory where iron is sequestered as ferritin to be stored in cells to prevent utilisation by pathogens for growth. Inflammatory cytokines may reduce EPO production or the bone marrow’s responsiveness to EPO.
It is the most common type of anaemia in admitted hospital patients.
Clinical signs include pallor, heart murmur, angina and fatigue.
18
Q
Which conditions are associated with anaemia of chronic disease?
A
Infections such as viral and chronic
Cancer
Autoimmune diseases
CKD and inflammation
19
Q
What are the indictors on FBC of anaemia of chronic disease?
A
There will be reduced Hb and MCV, but MCV can also be normocytic. There will be a high serum ferritin but low serum iron.
20
Q
What are the types of thalassemia?
A
- Thalamseemia is a defect in the globin chain of haemoglobin, split into alpha and beta thalassemia. The Hb are insoluble and precipitate in the RBCs, causing the spleen to initiate haemolysis and leading to ineffective erythropoeisis. It is divided into:
- Alpha thalassemia
- Beta thalassemia
21
Q
What is alpha thalassemia?
A
Alpha thalassemia is associated with a defect in either of the 4 alleles, and defect in one is asymptomatic while defect in all 4 results in hydrops fetalis, with severe swelling of the newborn.
22
Q
What is beta thalassemia?
A
Beta thalassemia results from point nonsense mutations and can be heterozygous and cause minor Microcytic anaemia Homozygous beta thalassemia causes severe anaemia, with only alpha haemoglobin remaining and causing precipitating of RBCs and inducing haemolysis, eventually leading to jaundice and hepatosplenomegaly
23
Q
What is sideroblastic anaemia caused by?
A
Deficiency in haem synthesis of protoporphyrin. failing to combining with Fe (iron) to make haem + globin -> haemoglobin. Therefore, there is failure to incorporate iron into haemoglobin.
24
Q
What does FBC show for sideroblastic anaemia?
A
Blood count shows low Hb, MCV and a rise in iron due to defect in protoporphyrin. There is a high ferritin and RDW.
25
What is aplastic anaemia?
There is a hypocellular bone marrow which is replaced by adipose tissue, that results pancytopenia where there is a reduction in RBC, WBC and platelets.
Blood count will show low RBC, reticulocytes Hb and MCV is normal. Bone marrow biopsy will be dry in the later stages but show hypocellular bone marrow with high fat content and absence of megakaryocytes.
26
What is the cause of aplastic anaemia?
Idiopathic is the most common
Franconia anaemia, an inherited disorder of DNA repair in the bone marrow
Medical interventions like radiotherapy and chemotherapy
27
What is spherocytosis?
Spherocytosis is a type of normocytic anaemia caused by an abnormality in RBC membrane protein, caused by a heterozygous or homozygous mutation in the ankyrin and/or spectrum protein that causes RBC to be smaller and spherical and affects its ability to deform and travel in the bloodstream. This can result in haemolysis in the spleen, causing asymptomatic splenomegaly and can progress to jaundice and an aplastic crisis, where marrow suppression occurs during viral infection.
28
What are the key features of spherocytosis on investigation?
High reticulocyte count occurs to make up for haemolysis. Patients will have low Hb, greater MCHC due to spherical smaller shape of RBC and high RDW and reticulocytes. Smear will show spherical RBCs with no central pallor. Tests include osmotic fragility test for tendency of RBC breakdown in hypotonic solution and EMA-3-binding protein
Assay .
29
What is the glucose-6-phosphate deficiency?
Glucose-6-phosphate deficiency isan autosomal recessive condition where deficiency in the molecule reduces the generation of NADPH which protects RBCs from oxidative stress.
This results in intravascular haemolysis due to oxidative triggers like infections or fava beans (falafel) causing haemolytic jaundice and normocytic anaemia
30
What can cause sickle cell disease?
A substitution mutation from glutamine to valine in the globin chain. This results in polymerisation of the B globin chain, resulting in Ca2+ influx into RBC and H20 and K+ efflux, causing RBC dehydration and a rise in Hb level, resulting in hepatosplenomegaly due to haemolysis. The defective haemoglobin tends to precipitate and polymerise in low oxygen vessels like the veins, causing a venoocclusive crises due to impaired tran, resulting in ischaemia and pain. Deoxygenated haemoglobin will increase with volume depletion, acidosis and hypoxaemia.
31
What is the treatment for sickle cell anaemia?
* Blood transfusions
* Regular screenings
* Hydroxyurea which increases the levels of HbF to cause oxygen disassociation curve to shift to the left and prevent polymerisation of sickle cell RBC.
* Daily folic acid supplements due to high rate of erythropoeisis to compensate for dysfunctional RBCs
* Splenectomy and prophylactic penicillin and vaccination
32
What is priapism?
Priapism can occur with sickle cell disease, where the penis remains erect for a prolonged period without stimulation due to ischaemia.
33
What are the symptoms of normocytic normochromic anaemia?
* Fatigue
* Palpitations
* Headaches
* Dyspnoea
* Jaundice
* Dark urine
34
What is pure red aplasia?
Pure red cells aplasia is when the blood cell line for erythropoeisis in the bone marrow is disrupted, and this is commonly associated transiently with parvovirus, especially in those with sickle cell. This results in low Hb, low reticulocyte and normal MCV. PRA can also occur due to:
->Autoimmune conditions such as rheumatoid arthritis
antibodies
-> Diamond Blackman syndrome which is hereditary due to defective ribosome synthesis.
35
What are the clinical features of normocytic normochromic anaemia?
Autoimmune haemolytic anaemia is characterised by a triad of jaundice, splenomegaly and low haemoglobin, with blood film showing spherocytes.
Symptoms of normocytic normochromic anaemia include fatigue, palpitations, headache, dyspnoea, jaundice and dark urine. Signs include pallor, splenomegaly, gallstones and leg ulcers.
36
What is warm haemolytic anaemia?
Warm haemolytic anaemia where there is IgG coating on the RBC, inducing splenomegaly. This can be diagnosed through the direct Coombs, There is a low Hb and Hct with a high reticulocyte count and lactate hydrogenate and low haptoglobin. Haptoglobin is a protein produced by the liver which reduces excess RBC outside RBCs and is low when there is excessive destruction of RBCS.
It can result in Evan’s syndrome, where there is autoimmune haemolytic anaemia and idiopathic thrombocytopenia.
37
What is the treatment of warm haemolytic anaemia?
Treatment of warm autoimmune haemolytic anaemia is cross-match test to provide intentionally incompatible blood transfusion to the patient.
Prednisone to reduce inflammation, rituximab to inhibit plasma cell action and haematopoietic stem cell transplant.
38
What is cold haemolytic anaemia?
Aka Cold agglutin disease is very rare and a condition characterised by IgM antibodies coating the RBCs, casing agglutination and resulting in splenomegaly, causing jaundice and a triad with splenomegaly and low haemoglobin.
39
What is the direct Coombs test used for?
To detect antibodies on the surface of RBC in order to diagnose autoimmune haemolytic anaemia.
40
What is the relationship between folate deficiency and DNA synthesis?
Folate deficiency results in impaired DNA synthesis, causing pancytopenia.
41
Which drugs inhibit folate?
Methotrexate, 5-fluorouracial, trimethoprim, PPIs and phenyotoin. Phenytoin inhibits the conjugate enzyme in food for folate absorption.
42
What are the symptoms of B12 deficiency?
* Glossitis
* Yellow skin
* Jaundice
* Angular cheilitis: sores around the mouth
Full blood count:cLow Hb and high MCV with low B12 and high serum homocysteine. There is pancytopenia due to impaired DNA synthesis so low WBC and platelets. Treatment is Intramuscular B12 injections
43
What is the cause of B12 deficiency?
-> the autoimmune disease pernicious anaemia, where damage to parietal cells causes impairment of intrisinnc factor release for absorption of B12 in the terminal ileum.
-> It can also occur due to chronic pancreatitis, because the intrinsic factor bound to B12 is not degraded by pancreatic enzymes, which prevents uptake
-> Crohn’s disease due to inflammation of the terminal ileum of the colon
-> Graves’ disease and Lupus
-> Carcinomas of the stomach and pancreas
44
What is the primary complication of B12 deficiency?
Subacute combined degeneration of the spinal cord, where demyelination occurs of the spinal cord in the dorsal column, leading to loss of propioception and the lateral corticospinal tract, causing spasticity. This is because B12 is important in synthesis of myelin and neurotransmitters in the spinal cord. This can also cause peripheral neuritis and dementia and psychosis
45
What are the risk factors for haematological cancers?
* Radiation
* Multiple myeloma
* Hodgkin’s lymphoma
46
What characterizes acute leukaemia?
Immature cells (myeloblasts or lymphoblasts) that overcrowd the bone marrow. leading to pancytopenia with fatigue, infection risk and frequent bleeding. They undergo leukostasis by entering the peripheral bloodstream to metastasise throughout the body.
It is associated with painless lymphadenopathy and hepatosplenomegaly.
47
What is myelodysplasia associated with?
Myeloid cells and abnormal platelets
## Footnote
Myelodysplasia is a disorder caused by poorly formed or dysfunctional blood cells.
48
What condition is characterized by uncleared RBCs?
Myelofibrosis
## Footnote
Myelofibrosis involves the replacement of bone marrow with fibrous tissue.
49
What is electrophoresis?
Electrophoresis separates proteins based on electrical charge and identifies the presence of paraproteins.
50
What is immunofixation?
Immunofixation uses antibodies to determine which component is responsible for the M spike in electrophoresis e.g anti-IgA antibodies will identify IgA
51
How does urine dip test detect paraproteins?
Urine dip test can’t be used to detect paraproteins because it only detects albumin based proteins. Therefore, it is based on electrophoresis, where it separates plasma proteins out based on their charge, and shows an M spike in multiple myeloma, indicating monoclonal cells associated with cancer.
52
What is the most common leukaemia in adults?
Acute myeloid leukaemia (AML) that occurs in 40-65 year olds.
Lymphadenopathy rarely occurs and it is characterised by pallor, easy bruising, infections and hepatomegaly.
## Footnote
It affects the myeloid lineage producing erythrocytes and granulocytes.
53
What genetic mutation is commonly associated with AML?
Chromosomal translocation between chromosome 8 and 21
## Footnote
This mutation is a diagnostic marker for AML with a good prognosis.
54
What are common causes of AML?
* Chromosmal translocation between Chrosmome 8 and 21
* Chemo radiation
* Genetic conditions (Down’s, Turner’s, Klinefelter’s)
* Myelodysplasia syndrome
* CML
*Myeloproliferative disorders
*Myelodysplasia
55
What are the myeloproliferative disorders?
Disorders of the bone marrow that lead to excessive replication, including:
Polycythaemia
Essential thrombocytosis
Myelofibrosis with metaplasia
There is excess extramedullary haematopoesis in the spleen and liver, and induce reactive bone marrow fibrosis that can TRANSFORM to AML.
56
Which subtype of AML is associated with Down’s syndrome?
Acute promyelocytic leukaemia, caused by a translocation with the chromosome 15 and 17, causing a fusion of the PML-RARA gene that promotes cellular proliferation. This is associated with Down’s syndrome. There is excessive activation of extrinsic factor for clotting and fibrinolysis, which increases clotting risk.
## Footnote
It is caused by a translocation between chromosomes 15 and 17.
57
What indicates a good prognosis in AML?
Inversion of chromosome 16
Chromosomal translocation between 8 and 21
Chromosmal translocation between 15 and 17
## Footnote
Other chromosomal abnormalities like inversion of chromosome 3 or monosomy 7 indicate a bad prognosis.
58
What indicates a poor prognosis in AML?
Chromosomal translocation between 6 and 9
Inversion of chromosome 3, monosomy 7 or 5q deletion has a bad prognosis
59
What is the pathophysiology of AML?
Excessive myeloblasts invade the bone marrow, causing pancytopenia and causes expansion of the bone marrow, leading to bone pain. Systemically, there is a rise in leukocytes and leukostasis occurs which causes ischaemia to vital organs, like eyes (vision loss), brain (ischaemic stroke of the brain) and shortness of breath (lungs).
The abnormal leukocytes from myeloblasts can invade the epidermis/dermis and cause cutaneous lesions with red lesions over the skin and they invade the gums, causing Gingivial hyperplasia.
60
How is AML diagnosed?
* Peripheral blood smears show myeloblasts
* Immunophenotyping shows positive for myeloperoxidase and negative for TDT.
* Bone marrow biopsy showing greater than 20% of bone marrow is occupied by myeloblasts. There will be pink Auer rods bound to myeloblasts, which is crystallisation of myeloperoxixdase enzymes -> very common in APL
* FBC showing anaemia and thrombocytopenia with either high or low WBC.
* Cytogenetic to assess for chromosomal abnormality
61
What is TDT?
TDT is a diagnostic marker for immature B and T lymphocytes and is raised in ALL and low in AML.
62
Which conditions are associated with Auer rods?
AML
CML in the blast phase
Myelodysplasia
63
What is the treatment of AML?
Haematopoietic stem cell transplant
Intensive chemotherapy based on 3 cycles
->Induction chemo to put the cancer into remission
->Consolidation to eliminate any residual disease
->Maintenance
Bone marrow transplant for failed chemotherapy
Chemotherapy with doxorubicin and intrathecal prophylactic methotrexate use
64
How is leukostasis treated in AML?
Treatment for leukostasis causing ischaemia is cytoreduction (removal of tumour) using hydroxyurea which inhibits myeloblasts replication or leukophoresis to remove WBCs from bloodstream.
65
What are the complications with chemotherapeutic treatment?
Tumour lysis syndrome, A condition that occurs with the treatment of myeloblasts, releasing excessive potassium, uric acid, and phosphate causing kdiney tubule damage. The high phosphate combines with calcium and form kidney stones and uric acid can create kidney stones, leading to renal disease.
## Footnote
This can lead to kidney tubule damage and kidney stones.
66
What are the electrolyte imbalances in tumour lysis syndrome?
Hyperuricaemia
Hypocalcaemia
Hyperkalemia
Hyperphosphataemia
67
How is tumour lysis syndrome treated?
Tumour lysis syndrome is treated with allopurinol to prevent complications with high uric acid by inhibiting xanthine oxidase and hydration with IV fluid to prevent kidney stone formation
68
What is the characteristic of chronic myeloid leukaemia (CML)?
Small and mature myeloid cells, typically dysfunctional neutrophils Patients are older and onset is more insidious. It tends to affect 40-60 years old, like AML.
## Footnote
CML often affects older adults with an insidious onset.
69
What genetic abnormality is commonly found in CML?
Translocation between chromosome 9 and 22, resulting in the BCR-ABL protein that is a tyrosine kinase which is an oncogene that promotes proliferation.
## Footnote
This protein is a tyrosine kinase that promotes proliferation.
70
What are the clinical features of CML?
and painless lymphadenopathy and abdominal pain with splenomegaly. It can metastasise to the spleen and cause infarction, which can be heard with a stethoscope with friction rub.
There will be normocytic anaemia due to malignancy, resulting in high lactate dehydrogenase and Uric acid. There is high platelet count (thrombocytosis) and WBC. Basophilia occurs in the later stages. Bone marrow biopsy shows hyper cellular myeloid hyperplasia.
71
What are the phases of CML?
* Chronic phase
* Accelerated phase
* Blast crisis
72
What happens in chronic phase of CML?
where patient is asymptomatic and there is a predominance of abnormal mature myeloid cells, particularly WBCs and basophils are a key feature that rises. These deposit into the spleen and cause extramedullary haemotopoeisis, leading to splenomegaly and causes earlier satiety Patients will be highly responsive to treatment. Basophils will induce fever and night sweats. In this phase, thrombocytosis can occur but RBCs are not yet affected
73
What happens in the accelerated phase of CML?
There is a rise in myeloblasts and splenomegaly with risk of splenic rupture and basophilia, causing pruiritis. Anaemia symptoms present here typically and thrombocytopenia occurs, causing epistaxis and increased bleeding. High infiltration of bone marrow by myeloblasts can cause bone pain.
74
What happens in the blast phase of CML?
High number of myeloblasts in the peripheral blood and CML will typically progress -> AML.
Basophilia produce histamine and promotes pruiritis, diarrhoea and flushing.
In the blast phase, patients are unresponsive to treatment and there is worsening of bone pain, thrombocytopenia and anaemia. Increased infection due to loss of functional WBCs and leukostasis and tumour lysis syndrome can occur.
75
What is an electrolyte complication with high cell turnover in cancer patients?
The high cell turnover results in hypophosphataemia over time, because phosphate is contained within cells. Symptoms of hypophosphataemia are trouble breathing, muscle weakness and loss of appetite.
76
What is the treatment of CML?
Treatment for CML is imatinib, a tyrosine kinase inhibitor and allergenic stem cell transplant. Alternative treatments may include chemotherapy like vincristine and prednisolone and cytarabine,
77
What is the most common childhood cancer?
Acute lymphoid leukaemia (ALL) It is characterised by lymhpoblasts affecting the lymphoid lineage of lymphocytes and dendritic cells.
Lymhpoblasts have no granules, scanty cytoplasm and high nucleus to cyptoplasm ratio.
## Footnote
It is characterized by lymphoblasts affecting the lymphoid lineage.
78
What is the aetiology of ALL?
ALL is characterised by a high number of lymphoblasts due to:
* Chemo radiation from treatment of previous cancer
* Down’s syndrome, with chromosomal translocation between 12 and 21 and is the most common type of acute lymphoid leukaemia and occurs in children.
* Philadelphia chromosome, between chromosome 9 and 22, forming BCR-ABL that promotes cellular proliferation and occurs in adults
* T cell acute lymphoid leukaemia occur because of a human T lymhpotrophic virus (HTLV)
79
What is the pathophysiology of ALL?
Systemically, the lymphoblasts will induce extramedullary haematopoesis and cause hepatosplenomegaly and abdominal fullness. Lymphadenopathy occurs due to lymphoblasts deposition and this also deposits in the meninges, causing meningitis presentation with photophobia and headache. This can compress CN VI and cause cranial nerve palsy where patient can’t abduct the eye. Leukostasis can occur and tumour lysis syndrome is a complication and cause renal failure.
80
What are the classifications of ALL?
* Pre-B ALL
* B cell ALL
* T cell ALL
81
What are the genetic mutations in Pre-B ALL?
Pre-B ALL is associated with Down’s syndrome in children. Translocation of chromosome 9 and 22 has a bad prognosis. Translocation with 12 and 21 has a good prognosis.
82
What are the genetic mutations in B cell ALL?
B Cell ALL is associated with translocation of
* Chrosmome 8 and 14, assoicated with Burkitt’s lymphoma
* Chromosome 8 and 22
* Chromosome 2 and 8
83
What is the cause of T cell ALL?
T cell ALL is more common in adults, associated with HTLV virus and T cell lymphoblasts deposit in the thymus which can enlarge and compress Oesophagus causing dysphagia, trachea, causing dyspnoea and SVC, causing SVC syndrome. pleural effusion and sleep apnoea.
84
What are the indicators for poor prognsois for ALL?
Poor prognosis for ALL: Age over 60, low WBC, mature B cell or T cell type, Philadelphia chromosome and translocation of chromosome 4 and 11 which is the MLL-AF4 fusion gene.
85
What are the indicators for good prognosis in ALL?
Young children, pre-B type, and translocation with chromosome 12 and 21
86
What are common markers for diagnosing ALL?
ALL will show low platelets, RBCs and normocytic or Macrocytic anaemia due to folate deficiency from rapid cell turnover, pancytopenia
Peripheral blood smear will show lymphoblasts.
Immunochemistry shows it is TDT positive which indicates immature B and T lymphocytes and MPO (myeloperoxidase) negative.
Flow cytometry use cluster of differentiation (CD) to indicate if it is a B or T cell ALL.
87
How is ALL treated?
Treatment for acute lymphoid leukaemia is chemotherapy based on CVAD.
C=cyclophosphamide
V= vincristine
A= asparaginase
Doxorubicin and dexamethasone
Prophylaxis is Intrathecal chemotherapy with methotrexate, cytarabine and steroids
88
What is chronic lymphocytic leukaemia (CLL) characterized by?
Accumulation of functionally incompetent mature lymphocytes, showing as smudge cells on blood smear with a mutation of ZAP70. This commonly occurs in over 70 year olds and can undergo Richter’s transformation to -> lymphoma. Patients are typically asymptomatic and diagnosed through routine bloods. It affects the lymphoid lineage, causing anaemia and splenomegaly.
## Footnote
CLL commonly affects individuals over 70 years old.
89
What are the pathological effects of CLL?
The lymphocytes are incompetent and cannot produce plasma cells, resulting in hypogammaglobinnaemia, increasing risk of infection. These lymphocytes overcrowd the bone marrow, causing pancytopenia.
Lymphocytosis has systemic effects and induces fever and night sweats by producing IL-1 and TNF-alpha.
Extramedullary haematopoesis causes hepatosplenomegaly.
The abnormal Lymphocytes may produce autoantibodies and result in autoimmune haemolytic anaemia and immune thrombocytopenia purpurin, called Evan’s syndrome which worsens already low levels.
The high number of lymphocytes increases viscosity and result in hyperviscosity syndrome, with the triad of vision loss, headache and anaemia.
90
What is the cause of CLL?
Unknown aetiology causes genetic mutations.
91
What is the Rai staging system for CLL?
* Stage 0: Lymphocytosis
* Stage 1: Lymphocytosis with adenopathy
* Stage 2: Lymphocytosis with lymphadenopathy and hepatosplenomegaly
* Stage 3: Anaemia + lymphocytosis lymphadenopathy and hepatosplenomegaly
* Stage 4: Thrombocytopenia + anaemia + lymphocytosis + lymphadenopathy and hepatosplenomegaly
92
What are the principles for treatment of CLL?
Earlier stages where it is asymptomatic is managed through watchful waiting.
Symptomatic Stage 1/2/3/4 is chemotherapy based on age.
Younger patients receive FCR:
-> Fludarabine
-> Cyclophasphamide
-> Rituxmab
Older patients receive ibrutinib.
Prednisolone can be given as a steroid to inhibit inflammation and can treat autoimmune haemolytic anaemia.
93
What is a complication with CLL?
Lymphoblasts accumulate in the lymph nodes and cause lymphadenopathy called small lymphocytic lymphoma, that can progress and form a core of lymphocytes in the lymph node, creating a diffuse B cell lymphoma by undergoing Richter’s transformation.
Richter’s transformation, CLL transforms into a more aggressive cancer like Hodgkin’s lymphoma or diffuse B cell lymphoma.
Blast crisis can cause conversion -> ALL.
94
What is a common treatment for CLL?
FCR: fludarabine, cyclophosphamide, and rituximab
## Footnote
Older patients may receive ibrutinib.
95
How is CLL diagnosed?
Flow cytometry for CD to determine which lymphocyte is affected, which is majorly B cells. B-CLL will show CD5, CD19 and CD20.
FBC shows anaemia, thrombocytopenia, neutropenia and lymphocytosis
Peripheral blood smear will show smudge cells
Bone marrow biopsy showing are small mature lymphocytes
96
What are myeloproliferative neoplasms?
Disordered cell growth of the myeloid lineage, typically affecting the elderly. This includes:
Essential thrombocytosis
Polycythaemia Vera:
Myelofibrosis with metaplasia
## Footnote
Examples include essential thrombocythemia and polycythemia vera.
97
What is the clinical presentation of polycythaemia?
Itchy skin in hot weather, excessive bleeding, high turnover causes high uric acid and kidney stones and gout, and splenomegaly. Treatment includes venesection to remove blood, allopurinol to prevent gout and chemotherapy. Investigations show high RBCs, Hb and B12 with low MCV and ESR.
98
What is the clinical presentation of essential thrombocytosis?
Essential thrombocythaemia causes excessive platelet production in the bone marrow due to a JAK2 mutation. This increases the risk of thrombosis, bleeding adn hyperviscisity syndrome with vision loss (tortuous retinal vessels) neuropathy and excessive bleeding. Treatment for essential thrombocythaemia includes aspirin to prevent blood clotting, hydroxyurea and interferon alpha to inhibit platelet formation and there is a risk of malignant transformation to AML and myelofibrosis and platelet pharesis.
Investigations for essential thrombocythaemia is hypercellular marrow, high RBC, High Hb, low MCV.
99
What is primary myelofibrosis
Myeloproliferative neoplasm where there is a hyper cellular marrow due to hyperplasia of megakaryocytes due to clonal malignancy of the megakaryocyte that stimulates excessive fibroblast production, leading to fibrosis of the bone marrow by type 3 collagen. Angiogenesis and osteosclerosis occurs due to the fibrosis.
Primary myelofibrosis is associated with a JAK-2 mutation that causes excessive stimulation of EPO and TPO. This causes excessive abnormal megakaryocte growth as a result of overexpression or over activation of TPO receptors. These abnormal megakaryocytes produce cytokines like growth factor that recruits fibroblasts and causes collagen deposition.
100
What mutation is associated with primary myelofibrosis?
JAK-2 mutation
## Footnote
This causes excessive stimulation of erythropoietin (EPO).
101
What mutation is associated with primary myelofibrosis?
JAK-2 mutation
102
What are the consequences of extramedullary haematopoiesis?
Hepatomegaly and splenomegaly
->The excessive action by the liver results in bile stasis and a rise in ALP. Splenomegaly can extend into the left costal margin and compress the stomach, leading to early satiety, and ascites which increases the risk of abdominal infection. In the later stages, extramedullary haematopoesis is ineffective in the liver and spleen, and the spleen causes destruction of RBCs and tr=hrombocytopenia occurs, causing anaemia.
103
What symptoms can splenomegaly cause?
Early satiety and ascites
104
What is a major risk associated with high cell turnover in myelofibrosis?
Gout attacks
105
What is essential thrombocythaemia characterized by?
Excessive platelet production
106
What mutation is associated with essential thrombocythaemia?
JAK2 mutation
107
What treatment is commonly used to prevent blood clotting in essential thrombocythaemia?
Aspirin
108
What are the symptoms of myelofibrosis?
Anaemia, pale skin, unintentional weight loss, night sweats, early satiety, bone pain, splenomegaly
109
What complication can hepatomegaly cause?
Portal hypertension
110
What are the characteristic features of myelofibrosis observed in a peripheral blood smear?
Nucleated RBCs with tear drop shapes and varied size aniccytosis) and high levels of LDH, ALP and uric acid. B12 will be high due to high neutrophil size. There is later dry tap on marrow aspiration which is inaspirable and has a high level reticulin collagen. X ray will show osteosclerosis.
111
What is the initial phase of myelofibrosis called?
Panmyelosis
112
What are the triad symptoms of hyperviscosity syndrome in myelofibrosis?
Mucosal bleeding, retinal disturbances, neurological disturbances
113
What is the best treatment for myelofibrosis?
Steroids to inhibit fibroblasts
Splenectomy
Allopurinol which inhibits xanthine oxidase for uric acid formation.
Chemotherapy with prednisone and low dose thalidomide.
Allogenic bone marrow transplant
114
What is secondary myelofibrosis commonly associated with?
Conditions like polycythaemia and essential thrombocythemia
115
What are the diagnostic criteria for myelofibrosis?
Megakaryocyte proliferation, collagen throughout bone marrow, JAK2 mutation, leukoerythroblastosis, palpable splenomegaly
116
What is hypervisciosity syndrome?
Hyperviscosity is a triad of symptoms due to plasma viscosity over 2 mmol/L where
Visual disturbances occur due to tortuous retinal veins
Neuropathy due to reduced blood in the vasa vasorum to the nerves, causing confusion, dizziness and stupor
Increased bleeding time and propensity to bleeding due to congested and engorged vessels
117
What are the types of hyperviscosity syndrome?
The 3 types of hyperviscosity syndrome is
Serum hyperviscosity due to high levels of paraproteins from cancers like myeloma
Polycythaemia hyperviscosity or leykocytosis
Red blood cell deformity due to sickle cell anaemia
Hyperviscosity is treated with blood drawing or removing the plasma or WBCs and providing hydration to patient.
118
Which biopsy is used to diagnose lymphoma?
Excisional biopsy
119
What are Reed-Sternberg cells associated with?
Hodgkin’s lymphoma
-> It starts in the supracervical and anterior mediastinal lymph nodes and is associated with CD15 and CD30 B lymphocytes, typically triggered by Epstein Barr virus infections, which cause a mutation of the transcription factor nuclear factor kappa B.
There is a bimodal age distribution at 15 and a later peak in late adulthood. Hodgkin’s causes a localised contagious spread of lymphadenopathy which is painless, rubbery and contiguous (continuous).
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What is the pathophysiology of Hodgkin’s lymphoma?
Hodgkin’s lymphoma occurs where centroblasts that are non functional do not get negatively selected and enter apoptosis. This can occur due to a mutation in the nuclear factor kappa, a transcription factor that regulates apoptosis. These transcription factors can be altered in HIV and Epstein-Barr virus, resulting in centroblasts where there are giant cells with large multinucleated nucleus called Reed Sternberg cells which accumulate in the lymph nodes.
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Which lympho nodes are typically affected in Hodgkin’s lymphoma?
Cervical, supraclavicular, axillary and mediastinal lymph nodes are affected.
Mediastinal lymph nodes can compress the heart, lungs and SVC, causing SVC syndrome and causing coug and shortness of breath (lung compression) and chest pain (pericardium/pleura compression)
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What is the age affected in Hodgkin’s lymphoma?
Bimodal age distribution with First peak at age 15-34 and second peak at age 50
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What are the complications with Hodgkin's lymphoma?
It can progress to acute lymphoid leukaemia and result in secondary amyloidosis, leading to nephrotic syndrome.
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What is the most common type of Hodgkin’s lymphoma?
Nodular sclerosis which typically happens in women and children. It begins in the anterior mediastinal lymph nodes have reed-sternburg cells with a lacunae (empty space). It has an excellent prognosis.
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Which type of Hodgkin’s occurs more in the elderly?
Mixed cellular is more common in the elderly but also in children, triggered by HIV and begins in the abdominal lymph nodes and spleen. It is characterised by plasma cells and eosinophilia.
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What are the features of lymphocyte rich Hodkgin’s lymphoma?
Lymphocytes rich Hodgkin’s lymphoma has the best prognosis and has CD15 and CD20 features.
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What are the features of lymphocyte depleted Hodgkin’s lymphoma?
Lymphocyte depleted is the least common subtype with the most aggressive cancer and poorest survival, associated with extranodal manifestations and AIDs. CD20 and CD45 are features.
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What are the characteristic markers for classical Hodgkin’s lymphoma?
CD15 and CD30
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What are the common symptoms of Hodgkin’s lymphoma?
Painless lymphadenopathy, painful lymphadenopathy when drinking alcohol, pruiritis, weight loss, night sweats, fever.
Pan-Ebestein fever
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What is Pan-Epstein fever?
Sporadic fever which increases then decreases over 1-2 weeks. IL-1, Il-6 and TNF-alpha are released from the tumour and acts on the hypothalamus, causing fever, night sweats and weight loss.
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What is the classification for Hodgkin?
Lugano system
Stage 1: lymph node on one side
Stage 2: 2 lymph nodes on same side
Stage 3: 2 lymph nodes on opposite sides
Stage 4: extranodal involvement Lymph node on one side
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What is the treatment for stage 1-2 Hodgkin’s lymphoma?
Doxorubicin, Dacarbazine, Vincristine, Bleomycin
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What is the treatment for advanced Hodgkin’s lymphoma?
Cyclophosphamide, Prednisone, Vincristine, Doxorubicin, Toposide
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What is an M protein?
M protein/paraprotein is produced due to abnormal plasma cells undergoing excessive monoclonal differenitation and causing a spike/rise in a singular type of immunoglobulin. IN the urine, these are known as Bence-Jones proteins.
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What are the two types of B cell lymphomas?
Aggressive B cell lymphomas and Indolent B cell lymphomas
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What are the diffuse B cell lymphomas?
-> Diffuse B cell,
-> Mantle B cell lymphoma
-> Burkitt’s
They are generally more aggressive and typically affect younger patients and are more sensitive to chemotherapy with curable however have a lower survival rate. And more B symptoms.
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What are the indolent B cell lymphomas?
-> Follicular lymphoma
-> MALT
-> CLL
They typically affect older patients and at a later stage of disease when diagnosed, with less sensitivity to chemotherapy but have a higher survival rate and less B symptoms.
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What is the most common type of non-Hodgkin’s lymphoma?
Diffuse B cell lymphoma associated with 65 year olds and arises from a genetic mutation or progression from an indolent lymphoma. It can compress structures in the mediastinum like the lungs, heart and SVC, causing SOB and chest pain.
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What is a marker of B cell lymphoma?
A non specific marker for diffuse B cell lymphoma is High levels of lactate dehydrogenase due to tumour cell glycolysis and high red cell turnover. This type of lymhpoma is the most common cause for CNS lymphomas.
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How is diffuse B cell lymphoma diagnosed?
Excisional biopsy
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How is diffuse B cell lymphomas treated?
Localised B cell lymphoma is treated with chemotherapy and radiotherapy
Advanced spread is treated with 6-8 cycles of chemotherapy and additional stem cell therapy for younger patients. Prophylaxis treatment for diffuse B cell lyphoma to the CNS is provided with ntrathecal chemotherapy and methotrexate.
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What is the general treatment for non-Hodgkin’s lymphoma?
RCHOP
Rituximab
Cyclophosphamide
H-doxorubicin
O- vincristine
Prednisone
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What is Burkitt’s lymphoma?
Burkitt’s lymphoma is more common in young males caused by a translocation between chrosmome 8 and 14 that results in the MYC proto-oncogene being in close proximity on chromosome 14 to the IgG promoter gene, resulting in over profileration. There are two types:
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What are the types of Burkitt’s lymphomas?
Endemic African subtype, characterised by lymphadenopathy with a jaw mass. This is assoicated with HIV.
Sporadic American subtypes, characterised by lymhpoadenopathy of the gut, pre-aortic and para-aortic lymph nodes. This results in abdominal distention and intr abdominal mass.
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What is a key feature of Burkitt’s lymphoma?
Starry sky appearance with neoplastic B cells and high levels of reactive histocytes macrophages attempting to clear dead cells.
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What is the common treatment for Burkitt’s lymphoma?
Intensive chemotherapy
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What is Mantle cell lymphoma?
Mantle lymphoma is an indolent B cell lymphoma caused by a chromosomal translocation between chronometer 11 and 14 that cause overexpression of BCL 1proto-oncogene. Immunochemistry will show positive for CD5 and negative for CD23. Mantle cell B lymphomas occur in the mantle off the cortex and tends to affect men over 65 years old.
It causes palpable painless lymphadenoapthy and frequent B symptoms.
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What chromosomal translocation is associated with mantle cell lymphoma?
Between chromosome 11 and 14
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What are the symptoms of mantle cell lymphoma?
Palpable painless lymphadenopathy and frequent B symptoms
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What is the treatment regimen for mantle cell lymphoma?
HCVAD: Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone
-> This is also used in ALL.
Ibruitinib, a tyrosine kinase to disrupts the B cell maturation process from pro-B cell to pre-B cell analysed by brutine tyrosine kinase.
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What is the most common indolent lymphoma?
Follicular lymphoma, caused by a chrosmomal translocation between chrosmome 14 and 18, resulting in BCL2 overexpression that leads to overexpression of BCL2. The overall architecture is disrupted and there is palpable painless lymphadenopathy.
It can cause pancytopenia and has lesser association with B symptoms.
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What is Ibrutinib?
A tyrosine kinase inhibitor that disrupts the B cell maturation process from pro-B cell to pre-B cell
## Footnote
Analyzed by brutine tyrosine kinase.
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What is the most common indolent lymphoma?
Follicular lymphoma
## Footnote
Caused by a chromosomal translocation between chromosome 14 and 18, leading to BCL2 overexpression.
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What are the key characteristics of follicular lymphoma?
* Painless lymphadenopathy
* Pancytopenia
* Lesser association with B symptoms
* Possible transformation into diffuse B cell lymphoma
## Footnote
Diagnosis via core needle or excisional biopsy showing B cells in a follicular pattern and Immunochemistry showing CD20.
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What is the treatment for localized follicular lymphoma?
Watchful waiting for asymptomatic patients.
Localised follicular lymphoma is treated with Radiotherapy.
Diffuse follicular lymphoma is treated with intensive chemotherapy and rituximab.
## Footnote
Asymptomatic cases may involve watchful waiting.
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What is marginal B cell lymphoma?
Marginal B cell lymphoma is a malignancy of B cells of the marginal zone of the lymph node, which can also occur in the extranodal lymph nodes like the stomach, salivary gland, intestines, bladder and the spleen.
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What are the risk factors for marginal B cell lymphoma?
Chronic inflammation from
* Hashimoto’s disease, that increases the risk for a thyroid lymphoma of the MALT and diffuse B cell lymphoma.
* Sjögren’s syndrome, autoimmune condition where there is destruction of the salivary and lacrimal glands, which increases the risk of extranodal salivary MALToma and diffuse B cell lymhpoma.
H.Pylori infection
## Footnote
These autoimmune conditions increase the risk for various lymphomas.
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What are the extranodal manifestations of marginal B cell lymphoma?
Chronic inflammation can also occur due to H.pylori infection, diagnosis from as tool sample and cause gastric MALTOMA
Epstein Barr virus
Borrelia burgdoferi that causes Lyme disease and leads to cutaneous mALTOMA
Chlamydia cases conjunctivitis and can lead to ocular MALTOMA
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How is marginal B cell lymphoma diagnosed?
Excisional core needle biopsy showing malignant B cells in the marginal zone, physical examination and CT scan of head, chest, abdomen and pelvis
Extranodal manifestations can produce organ specific symptoms, like dysphagia for GI tract and cough for lungs and splenomegaly.
Immunochemistry will show positive CD20
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What is the treatment for marginal B cell lymphoma?
Asymptomatic is based on watch and wait approach.
Localised treatment is with radiation
Diffuse: single agent chemotherapy like chlorambucil (alkylating agency) with rituximab.
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What is hairy cell leukaemia?
Hairy cell leukaemia is a subtype of chronic lymphoid leukaemia caused by a mutation in the BRAF1 gene at the V600E mutation, where aline is replaced with glutamic acid, resulting in overexpression of BRAF1 which promotes cell proliferation There is also cyclin D expression that promotes G1 -> S phase transition.
BRAF1 gene V600E mutation
## Footnote
This results in overexpression of BRAF1 promoting cell proliferation.
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What are the clinical features of hairy cell leukaemia?
It tends to affect middle aged Caucasian males. The lymphocytes accumulate, causing reticulin fibrosis and leads to cytopenia. Due to the fibrosis, bone marrow taps are typically dry.
Patients typically have splenomegaly, causing abdominal discomfort and early statistically and hepatomegaly due to extramedullary haematopoesis. Bone marrow can become crowded out by these cells and result in pancytopenia and loss of humoural and cell-mediated immunity. Cutaneous vasculitis is common and lymphadenopathy is rare.
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What does a blood smear of hairy cell leukaemia typically show?
Abnormal lymphocytes with cytoplasmic hairy projections These lymphocytes are trapped in their site of production in the spleen or bone marrow, so lymphadenopathy is rare. They stain positive for TRAP +
Flow cytometry will show positive for CD19, CD20 and CD22 due to B cell markers. It willl also be positive for CD103, CD11c and CD25.
## Footnote
These lymphocytes are often trapped in the spleen or bone marrow.
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What is the treatment for hairy cell leukaemia?
* Cladribine
* BRAF-1 inhibitors
* Supportive therapy
* Splenectomy
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What is multiple myeloma?
* Abnormal monoclonal proliferation of plasma cells
* Production of paraproteins due to a rise in a single immunogobulin IgA and IgG with excess of the immunoglobulin light chain, either kappa or lambda known as a paraprotein. These abnormal plasma cells crowd out other cells in the bone marrow, causing pancytopenia and release cytokines which disrupt the regulation of bone synthesis.
* Risk of transformation to Acute lymphoid leukaemia (ALL)
## Footnote
Leads to crowding out of other cells in the bone marrow causing pancytopenia.
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What is the criteria for diagnosing multiple myeloma?
CRAB
* Calcium high
* Renal insufficiency
* Anaemia
* Bone lesions
Investigations will show Anaemia, Increased urea and nitrogen ratio and high creatinne due to renal failure and Urinary Bence-jones proteins.
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What is the pathophysiology of multiple myeloma?
Plasma cells interact with bone marrow stromal cells that promote further proliferation, survival and migration and drug resistance of the monoclonal cells. The plasma cells produce
* IL-3 which inhibits osteoblasts activity.
* DKK1 which inhibit DPG for reducing osteolysis and it also inhibits osteoblast differentiation
* MIP1-alpha and Rank ligand increase osteoclast activity.
* IL-6 produced by osteoclasts which stimualtes RANKL for osteolysis.
These results in lytic punched out bone lesions in the vertebrae, ribs and skull compression fractures due to osteoporosis, that results in hypercalcaemia due to high levels of calcium, causing lethargy, confusion, muscle weakness and GI symptoms. and proteinuria.
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What are common complications of multiple myeloma?
* Hyperviscosity syndrome
* Loss of humoral immunity from B lymphocytes
* Renal tubular acidosis
* Proteinuria
* Dehydration
* Leukoerythroblastosis
## Footnote
Hyperviscosity syndrome can cause visual disturbances and increased bleeding time.
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What is the increased infection risk in multiple myeloma?
There is increased risk of infection by staphylococcus aureus, pneumoniae, E.Coli and haemophilius influenzae. There is no change in susceptibility to viruses because T cell function is maintained.
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How does multiple myeloma cause renal damage?
Hypercalcaemia which causes dehydration and increases formation of kidney stones which increases risk of infection along with loss of humoral immunity -> pyelonephritis
High levels of paraproteins which causes amyloid protein deposits and cause Bence Jones proteins which create tubular obstruction and proteinuria
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What is SVC syndrome?
SVC syndrome occurs where there is compression of the superior vena cava, typically due to lymphoma or lung cancers, resulting in reduced fluid removal from the upper body:
Facial oedema
Swollen neck and shoulders
Congested blood resulting in visible distended veins on the anterior chest wall
Fluid moving into the extracellular space, causing dyspnoea
Tachycardia and tachypnoea to compensate
Hypotension
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What is primary haemastasis?
Primary haemastasis involves platelet activation and adhesion, involving interactions between Von willebrand factor and Gpiia/iiib.
Disorders of primary haemastasis results in easy bruising, haemarthroses and gum bleeding. Conditions within this include:
Thrombocytopenia
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What is secondary haemastasis?
Secondary haemostasis involves clot mesh forming due to plasmin and fibrin mesh, as a result of clotting factors. This typically results in deeper bleeding. Conditions within this include:
Haemophilia A, Haemophilia B and Haemophilia C
Von willebrand disease due to factor VIII activatoin
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What causes generalised inability to clot?
General issues with haemastasis occurs due to liver disease or vitamin K deficiency, which is important in the activation of factor 2, 7, 9 and 10 that causes prolonged PT and PTT time.
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What is disseminated intravascular coagulation (DIC)?
Disseminated intravascular coagulation is an acquired condition characterised by initial thrombosis followed by haemorrhaging and bruising. This occurs due to the excessive release of tissue factor that promotes blood clotting, reducing space in vessels for RBCs to travel through, resulting in microangiopathic haemolytic anaemia. This can lead to ischaemia and tissue damage, especially of the endothelium. Over time, this excessive clot formation causes consumption of clotting factors and results in a deficiency which can lead to haemorrhage.
There is loss of activity of coagulation inhibitors like tissue factor inhibitor, Antithrombin, protein C and plasminogen which inhibit clot formation.
## Footnote
Caused by excessive release of tissue factor.
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What is the cause of DIC?
DIC occurs due to a range of conditions:
Obstetric complications
Cancers like Acute promyelocytic leukaemia and adenocarcinoma
Sepsis release TNF-alpha which promotes platelet clotting
Pancreatitis
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What is the primary defect in Hemophilia A?
Factor VII deficiency which is an X linked recessive condition. It begins with prolonged bleeding time that progresses onto haemarthroses, which is blood in the joint space. Blood entering the muscles can cauase a haematoma to form and result in compartment syndrome. It is the most common type of haemophilia where there is increased PTT time due to affecting the extrinsic pathway because of Factor VII deficiency.
## Footnote
An X-linked recessive condition leading to prolonged bleeding time.
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What is Von Willebrand factor important for?
Binding to GPiia/iiib for platelet adhesion and activation and Factor VIII activation. actvation for primary haemostasis in order to aggregate and form clots, resulting in thrombasthenia.
## Footnote
It is also crucial for factor VIII activation.
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What are the clinical features of Von Willebrand disease?
* Easy bruising
* Prolonged bleeding
* Possible joint bleeding
* Symptoms may appear in adulthood
## Footnote
Type 1 is an autosomal dominant disease with a partial defect.
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What is the treatment for Hemophilia B?
Factor IX or tranexamic acid
## Footnote
Tranexamic acid is an anticoagulant.
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What are some clinical features of systemic lupus erythematosus?
* Butterfly macular rash
* Joint pain
* Photosensitivity
* Oliguria
## Footnote
The kidneys are typically affected due to glomerulonephritis.
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What is the treatment for mild Hemophilia A?
Desmopressin
## Footnote
It raises the levels of Von Willebrand factor and Factor VII.
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What is the consequence of prolonged PT and PTT time?
Indicates issues with secondary haemostasis
## Footnote
Can occur due to liver disease or vitamin K deficiency.
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What causes hyperviscosity syndrome in multiple myeloma?
High levels of paraproteins
## Footnote
Leads to visual disturbances, confusion, and increased bleeding time.
185
What is the significance of the M spike in multiple myeloma?
Indicates monoclonal cells associated with cancer
## Footnote
Detected through electrophoresis.
186
What is the primary treatment for SVC syndrome?
Addressing the underlying cause
## Footnote
Often involves managing the compressing tumor.
187
What is the role of osteoblasts in multiple myeloma?
Express RANKL which interacts with RANK receptor on osteoclasts to induce osteolysis
## Footnote
Osteoblasts also produce OPG to inhibit this process.
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What is the common demographic for multiple myeloma?
Individuals over 70 and African Americans
## Footnote
The most common subtype is IgG kappa.
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What is Type 1 Von Willebrand disease?
Autosomal dominant disease, most common where there is a partial defect in the number of vWF that reduces platelet clotting that presents in adulthood.
190
What is Type 2A von Willebrand disease characterized by?
A qualitative defect where large vWF cannot bind to vWF
## Footnote
This leads to a reduction in platelet adhesion.
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What happens in Type 2B von Willebrand disease?
Mutant vWF has hyperfunctional affinity to platelets, causing it to be cleared from circulation along with bound platelets, leading to a drop in platelet count.
192
Define Type 2M von Willebrand disease.
A mutant vWF with low binding to GpIIb, preventing platelet adhesion and activation.
193
What is Type 2N von Willebrand disease?
A mutation in vWF that causes very low platelet affinity to factor VIII, resulting in symptoms similar to hemophilia A.
194
What is Type 3 von Willebrand disease?
An autosomal recessive condition and the rarest type with severely reduced vWF count.
195
What are the clinical presentations of von Willebrand disease?
Excessive bleeding, mucocutaneous bleeding, epistaxis, easy bruising, and excessive menorrhagia.
196
What does a prolonged PTT time indicate in von Willebrand disease?
Reduced activity in the extrinsic pathway for Factor VIII but normal platelet count.
197
What treatment options are available for von Willebrand disease?
Tranexamic acid to inhibit bleeding and desmopressin to raise vWF levels and factor VIII concentrate.
198
Which blood type has low von Willebrand factor levels?
Type O blood.
199
What is Anti-phospholipid syndrome?
An autoimmune condition with antibodies like lupus-anticoagulant that increases the risk of thrombi formation.
200
List complications associated with Anti-phospholipid syndrome.
* Miscarriage
* Venous thrombi
* Arterial thrombi
* Stroke
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Who is more commonly affected by Anti-phospholipid syndrome?
Women and younger adults.
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What is the primary management strategy for Anti-phospholipid syndrome?
Low dose aspirin; prophylactic aspirin and a vitamin K antagonist like warfarin after a thromboembolic event. Pregnant women should immediately be started on aspirin and additional heparin if they have obstetric complications.
203
Where is a bone marrow biopsy typically performed?
From the anterior superior iliac spine. It involves removing a portion of the liquid bone marrow and includes trephine to remove 1-2cm of the spongy tissue.
204
What is alloimmunization during pregnancy?
Maternal immune response against fetal RBCs due to foreign antigens, such as the rhesus factor.
205
What are allergic transfusion reactions?
Reactions occurring immediately due to blood group incompatibility or contamination, often associated with IgA deficiency. Overload of the transfusion product into the patient, this can cause oedema, and stimulate acute respiratory distress. Allergic transfusion reactions present clinically with pruritius, wheezing, hypotension and urticaria.
206
What symptoms are associated with allergic transfusion reactions?
* Pruritus
* Wheezing
* Hypotension
* Urticaria
207
What characterizes a hemolytic transfusion reaction?
Acute inflammatory response mediated by pre-formed IgM antibodies due to ABO blood group incompatibility.
208
What are the symptoms of a hemolytic transfusion reaction?
* Fever
* Tachycardia
* Tachypnea
* Hypotension
Intravascular haemolysis occurs in the blood vessels themselves in the spleen and liver, resulting in high level of bilirubin which causes jaundice and damages the liver, leading to h
209
What occurs during delayed transfusion reactions?
Hemolysis occurs after 24 hours, often due to sensitization from pregnancy or previous transfusions.
210
What is a febrile transfusion reaction?
A non-haemolytic transfusion reaction more common in children, due to inflammatory cytokine release from WBCs in donor blood. These accumulate in the product over prolonged storage or there is a type 2 hypersensitivity reaction directed against the HLA on WBCs in donor blood.
Symptoms start in 1-6 hours, clinically presenting with fever, headache, rigors,chills and flushing. This can be prevented with leukoreduction.
211
What is transfusion-related lung injury?
Most common cause of death in transfusion reactions- Acute lung injury following a blood transfusion, leading to fluid accumulation and pulmonary edema. This begins in minutes->hour, because stressors like sepsis or shock prime neutrophils
212
What causes transfusion-associated circulatory overload?
Volume overload due to rapid blood transfusion or transfusion of multiple products. It is characterised by acute respiratory distress with dyspnoea, peripheral oedema, hypertension and tachycardia. Patients with heart failure or kidney injury are at a greater risk for this condition.
213
How are blood transfusions determined?
it is guided by the levels of haemoglobin, where one unit of RBCs should be transferred din non urgent situations over 90-120 minutes to increase Hb by 10-15 g/L
214
215
What transfusions do patients with clotting disorders receive?
Fresh frozen plasma.
216
What is cryoprecipitate?
Concentrated fresh frozen plasma ideal for patients with hemorrhages and clotting disorders like hemophilia.
217
What should be administered with blood transfusions in patients with heart failure?
Furosemide to reduce the risk of transfusion-associated circulatory overload.
218
What are common causes of low hemoglobin in children?
* Hereditary conditions (sickle cell, thalassemia, hereditary spherocytosis)
* Iron deficiency
219
What are common causes of low hemoglobin in adolescents?
* Folate/B12 deficiency
* Iron deficiency
* Sickle cell
* Spherocytosis
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What is a common cause of low hemoglobin in the elderly?
Anemia of chronic disease.
