Haematology Flashcards
What do the terms haematocrit, anaemia and haemophilia mean?
- Haematocrit = percentage of RBCs in cellular component of blood
- Anaemia = reduced Hb, often due to iron deficiency. Two types: impaired production + increased haemolysis
- Haemophilia = inability to make blood clots due to factor VIII deficiency (Haemophilia A) or Factor IX (Haemophilia B), A more common
How is blood divided? What are its different components?
- Plasma component (55%):
- Plasma (55%) = mostly consists of water, with water, salt, glucose and proteins
- Cellular component (45%):
- White blood cells and platelets (1%) = part of the immune system (WBC) and responsible for clotting (platelets)
- Red blood cells (44%) = responsible for carrying O2 and CO2
What is the structure of erythrocytes? What is their lifespan? Where are they formed and removed? What is a reticulocyte?
- Simple cell, anucleate, discoid, biconcave disc
- Live for 100-120 days
- O2/CO2 carrier
- Contain haemoglobin and glycolytic enzymes
- Formed: adults = bone marrow of axial skeleton, children = all bones, foetus = liver, spleen and yolk sac
- Removed in spleen, liver, bone marrow + through blood tests
- Reticulocyte = immature RBC, not usually found in blood
What is the structure of haemoglobin? What is its role? What are the different types of haemoglobin?
- Tetrameric protein with 4 globin chains, each with haem group (porphyrin with Fe2+) = capable of reversibly binding oxygen
- Carries oxygen from the tissue to the lungs
- Several haemoglobin types:
- Haemoglobin: 2 alpha and 2 beta chains
- Foetal haemoglobin: 2 alpha and 2 gamma chains, means it has a higher affinity for oxygen
- HbA2: 2 alpha and 2 sigma chains
What is haemopoeisis? Where does this occur in adults and in an embryo? What do stem cells produce? How are RBCs, WBCs and platelets produced?
- Haemopoeisis = formation of new blood cells and platelets. Adults = precursors of mature cells derived from bone marrow of axial skeleton, but all bones in children. Embryos = in yolk sac, liver, spleen + bone marrow. Stem cells = pluripotent so can differentiate into RBCS, WBCs or platelets
- RBC production = erythropoeisis
- WBC production = myelopoeisis
- Platelet production = thrombopoeisis
What are the hormonal factors in erythropoeisis, myelopoeisis + thrombopoeisis?
- Erythropoeisis = hormonal stimulating factor = erythropoeitin, made in kidneys
- Myleopoeisis = hormonal factor = granulocyte-macrophage colony stimulating factor, will only stimulate production of myeloblastic WBCs + not lymphoid cells
- Thromobopoeisis = hormonal factor = thrombopoeitin, leads to production of megakaryocytes, which platelets bud from
What are platelets? Where do they originate from? What is the regulatory hormone? What are the two types of granules?
- Platelets = 2-5um, last 7-10 days, circulate in inactive form + anucleate and discoid but become spiculated with pseudopia once activated, form blood clots (coagulation cascade)
- Originate from megakaryocytes, 1 megakaryocyte = 4000 platelets = membrane blebbing process
- Regulatory hormone = thrombopoeitin - produced by liver + kidneys
- Plasma have 2 types of granules: alpha (coagulation factors, fibrinogen and other clotting mediators) and dense (ADP + platelet-activation mediators)
What are leukocytes? What are the two main groups? What is their role? What are the different types?
- Leukocytes = white blood cells
- Two main groups: granulocytes + agranuloocytes
- Both involved in immune response, innate = granulocytes, adaptive = lymphocytes
- Granulocytes:
- Neutrophil = most abundant WBC, phagocytic and release chemo- + cytokines to induce inflammation. Multi-lobed nucleus, lasts ~10 hours. Granulocyte colony stimulating factor is the regulating hormone for most leukocytes (all the phils)
- Basophils = bi-lobed nucleus, very prominent dark blue granules of histamine, lasts 8-12 hours. Mature into mast cells, express IgE + release histamine. Mast cells are almost identical to basophils except are tissue-resident and come from a different cell lineage
- Eosinophils = bi-lobed nucleus that is ‘lozenge-shaped’, distinct granules, lasts 8-12 hours. Role in fighting parasitic infections but also wide range of regulatory functions
- Agranulocytes:
- Monocytes = reniform (kidney bean-shaped) nucleus, mature into macrophages (common macrophages you should know: Kupffer cells, alveolar macrophages, osteoclasts), lasts 8-12 hours
- Lymphocytes - ‘fried egg appearance’, comprise B and T cells (B cells mature in bone marrow, T cells mature in thymus gland). B lymphocytes = plasma cells/memory cells + produce antibodies, T lymphocytes = T helper, T cytotoxic, T suppressor. Lasts 8-12 hours
What is the role of Natural Killer cells? Where are T cells formed, where do they mature and what are the different types? Where to B cells form and mature, and what is their role?
- Natural Killer cells provide non-specific immunity against foreign proteins. They release perforins, which embed into the plasma membrane, creating channels and an influx of extracellular fluid which results in cell lysis
- T cells form in the bone marrow, but mature in the thymus. There are cytotoxic T cells, which directly attack infected cells, and helper T cells which activate the B cells and form memory T cells
- B cells form and mature in the bone marrow. They are involved in antibody secretion. B cells mature into plasma cells and memory B cells
What is plasma? Which proteins does it contain? What is serum?
- Plasma = fluid component of blood (55%)
- Transport medium containing water, salt, glucose + proteins
- Proteins:
- Albumin = produced in liver, determines oncotic pressure of blood, keeps intravascular fluid within that space, lack of albumin leads of oedema
- Carrier proteins
- Coagulation proteins. These are all produced by the liver
- Immunoglobins = produced by plasma cells, key role in immunity + vaccination
- Serum = plasma without clotting factors
What do all blood cells stem from? Where do these cells live?
- Multipotential haemopoietic stem cell (haemocytoblast)
- Haemotopoietic stem cells live in the bone marrow
What does the multipotential haemopoietic stem cell divide into? What do these two cells produce?
- Common myeloid progenitor and common lymphoid progenitor
- Common myeloid progenitor = platelets, erythrocytes, mast cells, basophils, neutrophils, eosinophils, monocytes
- Common lymphoid progenitor = lymphocytes (NK cells, T cells, B cells)
What is primary and secondary haemostasis?
- Primary haemostasis: initiation and formation of the platelet plug - platelet activation
- Secondary haemostasis: formation of the fibrin clot - intrinsic and extrinsic coagulation cascade
What happens in the platelet plug formation when endothelial cells lining the blood vessels are damaged? What happens when ADP and fibrinogen are released?
- Endothelial cells lining blood vessels damaged, exposes collagen underneath
- Healthy endothelial cells release Von Willebrand factors (VWF) that binds to exposed collagen
- Platelets arrive and have VWF receptor. They bind to VWF. This slows down platelets + causes them to become active
- Platelet activation causes platelets to change shape (smooth discoid to spiculated + pseudopodia) and causes them to express GbIIb/IIIa
- Platelets contain 2 types of granules: electron dense granules + alpha granules. Electron dense granules release ATP, ADP, serotonin + calcium and produce energy needed for reactions. Alpha granules release fibrinogen, VWF, platelet derived growth factor + heparin antagonist and are used to create mesh work to capture other platelets
- ADP released by electron dense granules and acts on P2Y1 + P2Y12 to cause platelet activation + amplification. Platelet activation results in increased expression of GbIIb/IIIa + they crosslink with other GbIIb/IIIa receptors on other platelets by binding to fibrinogen. Enables new platelets to bind to old ones = platelet aggregation = positive feedback
- Fibrinogen releases by alpha granules + binds to GbIIb/IIIa receptors. Needs to be turned to fibrin.
- Arachadonic acid can be converted to different products depending on COX enzyme. In presence of COX 1, converted to prostaglandin H2, then to thrombroxane A2. This activates prothrombin into thrombin. Thrombin turns fibrinogen into fibrin. Fibrin creates a network of mesh that captures other platelets
What inhibits:
a) thromboxane formation
b) P2Y12 binding
c) thrombin?
a) NSAIDs
b) clopidogrel/ticagrelor
c) dabigatran
What is the coagulation casacade? What are the vitamin K dependent procoagulant factors? Draw it out.
- Process of blood clotting, not be confused with platelet plug formation. Coagulation helps stabilise the plug. First protein = Factor XII, which activates Factor XI, which activates Factor IX etc. Ultimately soluble fibrinogen is converted to fibrin which then forms a stable fibrin clot.
- Intrinsic pathway = happens inside the blood, independent of the extrinsic pathway
- Extrinsic pathway = cannot happen without some of the proteins from the intrinsic pathway
- Vitamin K procoagulant factors: 1972. Factor 10, 9, 7 + 2
What can inhibit:
a) factor 9
b) factor 7
c) factor 10a
d) prothrombin (factor 2)
a) warfarin (blocks vitamin K)
b) warfarin (blocks vitamin K)
c) warfarin, rivaroxaban (directly), heparin
d) warfarin, heparin (via antithrombin III)
In a full blood count, what is indicative of neutropenia? How do we perform this? What are the causes of neutropenia?
- Neutropenia (low neutrophils) = < 2.0 x 10^9/L
- Do a blood film and repeat FBC in 4 weeks
- Causes:
- Infection (EBV, HIV, Hep B, Hep C)
- Drugs (Phenytoin, antipsychotics)
- Endocrine
- Malignancy (myeloma)
- Autoimmune
- Excess alcohol and liver disease
In a full blood count, what is indicative of neutrophilia? How do we perform this? What are the causes of neutrophilia?
- Neutrophilia (high neutrophils) = > 7.5 x 10^9/L
- Repeat FBC in 4 weeks
- Causes:
- Infection (bacterial, VZV, HSV) = most common cause
- Drugs (steroids)
- Malignancy (leukaemia, lymphoma)
- Rheumatoid arthritis
- Gout
- Hypoxia
In a full blood count, what is indicative of lymphopenia? What are its causes? How do we treat it?
- Lymphopenia (low lymphocytes) = < 1.3 x 10^9 L
- Causes:
- Drugs (steroids)
- Infection (post-viral = common)
- Malignancy
- Renal/hepatic impairment
- SLE, RA
- Anorexia nervosa
- Treat the underlying cause
In a full blood count, what is indicative of lymphocytosis? What number indicates an emergency? What are the causes of lymphocytosis?
- Lymphocytosis (high lymphocytes) = > 3.5 x 10^9/L
- If > 20x10^9/L refer urgently – emergency
- Causes:
- Infection (EBV, CMV, pertussis)
- Stress
- Vigorous exercise
- Malignancy
- Post splenectomy
In a full blood count, what is indicative of monocytosis? What are the causes of monocytosis?
- Monocytosis (high monocytes) = > 0.8 x 10^9 L
- Causes:
- Malaria
- Typhoid
- TB
- Myelodysplastic syndromes
In a full blood count, what is indicative of eosinophilia? How is the test performed? What are the causes? What should we check for when taking the patient’s history?
- Eosinophilia (high eosinophils) = > 0.44 x 10^9 L
- Do blood film and repeat FBC in 2 weeks
- Causes:
- Asthma
- PARASITIC INFECTIONS
- Drugs (penicillin, allopurinol, amitriptyline)
- Smoking
- Endocrine (Addison’s)
- Malignancy
- Endocarditis
- Post-splenectomy
In a full blood count, what is indicative of thrombocytopenia? What level indicate an urgent referral? What are the causes of thrombocytopenia?
- Thrombocytopenia (low platelets) = < 150 x 10^9/L
- If < 20 x 10^9/L refer urgently
- Causes:
- Viral infection (EBV, HIV, Malaria, TB)
- Drugs (NSAIDs, Heparin, Digoxin, PPIs)
- Alcohol
- Malignancies
- Liver and renal disease
- Aplastic anaemias
- SLE
In a full blood count, what is indicative of thrombocytosis? What level indicates an urgent referral? What are the causes of thrombocytosis?
- Thrombocytosis (high platelets) = > 400 x 10^9/L
- If >1000 x 10^9/L refer urgently – emergency
- Causes:
- Reactive (infection, inflammation, haemorrhage, post-surgery)
- Malignancies
- Splenectomy
- Iron deficiency
What is the PT/INR test? What is it used for? What are the normal times? What are the times affected by?
- PT/INR test = prothrombin time. The INR measures PT test over PT normal (+ a constant)
- The prothrombin time is a measure of the time taken for a blood clot to form via the EXTRINSIC pathway. Normal time = 12-13 seconds
- Normal INR time = 0.8-1.1
- Affected by liver disease, DIC, vitamin K deficiency and warfarin levels (too high)
What does aPTT measure? What is the normal range? Which conditions are linked with an abnormal aPTT?
- aPTT = partial thromboplastin time (35-45 seconds)
- It is the measure of the time take for blood to clot via the INTRINSIC pathway
- aPTT indicated issued with factors VIII, IX and XI
- The main conditions linked to this are:
- Haemophilia A (VIII)
- Haemophilia B (IX)
- von Willebrand’s disease (vWF pairs with factor VIII)
What does bleeding time assess and measure? What is the normal range? Which platelet specific disorders increase bleeding time?
- Bleeding Time (1-6 minutes) assesses overall platelet function and levels. It is a measure of how long it take a patient to stop bleeding from a wound
- Platelet specific disorders increase BT:
- von Willebrand’s disease
- ITP
- DIC
- Thrombocytopaenia
What does thrombin time measure? What is the normal range? What causes a prolonged time?
- Thrombin Time (10-15 seconds) tests how fast fibrinogen is converted to fibrin by thrombin
- If the time is prolonged, it is caused by either a synthetic issue or a consumption time:
- DIC
- Liver failure
- Malnutrition
- Abnormal fibrinolysis
What is multiple myeloma? What does it result in? How many excess immunoglobulins are there? What is it associated with? In which individuals is it most commonly found in?
- A malignancy of plasma cells
- The accumulation of malignant plasma cells in the bone marrow leads to progressive bone marrow failure. 55% excess IgG and 20% excess IgA
- Multiple myeloma is associated with the production of a characteristic paraprotein, kidney failure and bone disease
- Most common in adults > 75 and Afro-Caribbean people
In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is mono-clonality?
Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney
Suggest 3 ways in which multiple myeloma can lead to AKI.
- Deposition of light chain
- Hypercalcaemia
- Hyperuricaemia
In extreme cases, patients with myeloma can present with blurred vision, gangrene and bleeding. What is the pathology behind this?
Paraproteins form aggregates in the blood and change the viscosity
What disease often precedes myeloma? What is this disease?
- MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)
- A common disease with paraprotein present in the serum but no myeloma. Often asymptomatic. <10% plasma cells in the bone marrow
In approximately 2/3 of people with myeloma, what might their urine contain?
Immunoglobulin light chains with kappa or lamda lineage
Why are patients with myeloma susceptible to recurrent infections?
There is a reduction in polyclonal immunoglobulin levels
What are the symptoms and signs of multiple myeloma?
- Symptoms:
- Fatigue
- Infection due to neutropenia
- Signs (OLD CRAB):
- Old - over 75
- Calcium over 2.75 mmol/L = AKI
- Renal impairment
- Anaemia
- Bone lesions - pepper pot skull, back pain
Why is calcium elevated in myeloma?
There is increased bone resorption and decreased formation meaning there is more calcium in the blood
Why might someone with myeloma have anaemia?
The bone marrow is infiltrated with plasma cells. Consequences of this are anaemia, infections and bleeding
Why might someone with myeloma have renal failure?
Due to light chain deposition
What are the investigations for suspected myeloma?
- FBC - anaemia, raised ESR
- Blood film - ROULEAUX (aggregations of RBCs)
- Bone marrow biopsy - increased plasma cells
- Serum and urine electrophoresis - looking for a monoclonal protein band - BENCE JONES protein in urine
- X-rays - pepper pot skull, fractures
- CT - bone lesions, cord compression
What is the treatment for MGUS and asymptomatic myeloma?
Watch and wait
Describe the treatment for symptomatic myeloma.
- BISPHOSPHONATES for bones, e.g. Zoledronate
- Analgesia (avoid NSAIDs due to renal issue)
- Radiotherapy
- Blood transfusions
- Infection control (most common death)
- Chemotherapy: VCD, VTD and MTP
What type of disease is multiple myeloma? What is the aim for clinicians? What will happen near the end of the disease?
- Multiple myeloma is a palliative disease, so everyone will relapse
- The aim is to control the symptoms and neoplasia as best as possible to get the best quality of life for the patient
- At the end of the disease, end organ damage will occur:
- Lytic bone lesions
- Infection
- Fractures
- Renal failure
- Proteinuria
What is a lymphoma? Which organs may it affect?
- A malignant growth of T and B cells, predominantly in the lymph nodes (MAINLY B LYMPHOCYTES)
- Although predominantly in the lymph nodes, lymphomas may also affect:
- Blood
- Liver
- Spleen
- Bone marrow
What are the two classifications of lymphoma?
- Hodgkin lymphoma (aggressive and indolent)
- Non-Hodgkin lymphoma
How do we stage lymphomas?
- ANN-ARBOR staging is used for lymphoma
- I – Confined to a single lymph node region
- II – Involvement of 2 or more nodal areas on the same side of the diaphragm
- III – Involvement of 2 or more nodal areas on both sides of the diaphragm
- IV – Spread beyond the lymph nodes, e.g. bone marrow or liver
- Suffix A – No systemic symptoms other than pruritis (severe itching of skin)
- Suffix B – Presence of B symptoms, such as fever, night sweats and weight loss
Describe the pathophysiology of lymphoma.
There is impaired immunosurveillance and infected B cells escape regulation and proliferate (this is just a theory)
Give 4 risk factors for lymphoma.
- Primary immunodeficiency
- Secondary immunodeficiency, e.g. HIV
- Infection, e.g. EBV, HTLV-1
- Autoimmune disorders, e.g. RA
What is the epidemiology of Hodgkin lymphoma?
- BIMODAL (peaks twice in life) - EARLY 20S AND 70S
- Male predominance
- Associated with EBV, SLE, siblings
What is the difference between Hodgkin and non-Hodgkin lymphoma?
Hodgkin lymphoma is marked by the presence of REED-STERNBERG cells. In non-Hodgkin lymphoma, these cells are not present
What are the signs and symptoms of Hodgkin lymphoma?
- LYMPHADENOPATHY - painful nodes on drinking alcohol
- Systemic ‘B’ symptoms, e.g. fever, night sweats, weight loss
- Enlarged rubbery non-tendon nodes
What are the investigations for Hodgkin lymphoma? The presence of what cell confirms the diagnosis?
- FBC = anaemia, high ESR
- CXR/CT for staging
- LYMPH NODE BIOPSY - REED STERNBERG cells
How do we treat Hodgkin’s lymphoma?
- CHEMOTHERAPY ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine
- Radiotherapy
- Steroids
- Stem cell/bone marrow transplant
What is the treatment for stage 1 - 2A Hodgkins lymphoma? What is the treatment for stage 2B - 4 Hodgkins lymphoma?
- Short course combination chemotherapy followed by radiotherapy
- Combination chemotherapy
What are the possible complications of treatment for Hodgkin’s lymphoma?
- Secondary malignancies
- IHD
- Infertility
- Nausea
- Alopecia
What is the epidemiology of non-Hodgkin lymphoma?
- ADULTS 40+
- Associated with EBV + Burkitt’s lymphoma
- Family history increases risk
What are the signs and symptoms of non-Hodgkin lymphoma?
- Painless lymphadenopathy
- Systemic ‘B’ symptoms, e.g. fever, sweating, weight loss, fever
- Can get hepatosplenomegaly
What are the investigations for non-Hodgkin lymphoma?
- FBC - anaemia, high ESR
- Imaging (CT/CXR) for staging
- LYMPH NODE BIOPSY - NO REED-STERNBERG CELLS
- Raised lactate dehydrogenase
How do we treat non-Hodgkin’s lymphoma?
- If low grade and symptomless, do nothing
- RCHOP CHEMOTHERAPY: Rituximab, Cyclophosphamide, Hydroxy-danicorubicin, Vincristine, Prednisolone
- Steroids
- Monoclonal antibodies to CD20 - Rituximab
What is leukaemia? Name the four sub-types of leukaemia.
A malignant proliferation of haematopoeitic stem cells
4 sub-types:
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
- Acute lymphoblastic leukaemia
- Chronic lymphoblastic leukaemia
What is acute myeloid leukaemia? What is its epidemiology? What is it associated with?
- Acute myeloid leukaemia = neoplastic proliferation of MYELOBLASTS (become granulocytes)
- Seen in elderly (adults aged 40+). Progresses very rapidly; 20% 3 year survival. Medical emergency
- Associated with DOWN’S SYNDROME, haematological disorders and ionising radiation
What are the signs and symptoms of acute myeloid leukaemia?
- Anaemia - breathlessness, fatigue, pallor
- Infection
- Hepatosplenomegaly
- Bleeding and bruising
- GUM HYPERTROPHY
Why are anaemia, infection and bleeding symptoms of leukaemia? Why are hepatomegaly and splenomoegaly symptoms of leukaemia?
- Because of bone marrow failure
- Because of tissue infiltration
What are the investigations for acute myeloid leukaemia? What is diagnostic?
- BONE MARROW BIOPSY - AUER RODS
- FBC - anaemia, thrombocytopenia, neutropenia
- Blood film - leukaemic blast cells
Describe the treatment for acute myeloid leukaemia.
- Blood and platelet transfusions
- Chemotherapy
- Stem cell/bone marrow transplant
- Antibiotics
- Allopurinol to prevent tumour lysis
What is acute lymphoblastic leukaemia? What is its epidemiology? What is it associated with?
- Acute lymphoid leukaemia = uncontrolled proliferation of immature LYMPHOBLASTS (become NK cells and lymphocytes)
- MOST COMMON LEUKAEMIA IN CHILDREN AGED 0-4 YEARS
- Associated with DOWN’S SYNDROME and ionising radiation
What are the signs and symptoms of acute lymphoblastic leukaemia?
- CNS INVOLVEMENT - HEADACHES, CRANIAL NERVE PALSIES
- Anaemia - breathlessness, fatigue, pallor
- Bleeding/bruising
- Infection
- Hepatosplenomegaly
- Peripheral lymphadenopathy
What are the investigations for acute lymphoblastic leukaemia?
- FBC - anaemia, thrombocytopenia, neutropenia
- Blood film - leukaemic blast cells
- Lumbar puncture - CNS involvement
- CXR and CT - lymphadenopathy
Describe the treatment for acute lymphoblastic leukaemia.
- Blood and platelet transfusion
- Chemotherapy - METHOTREXATE
- Steroids
- Allopurinol to prevent tumour lysis syndrome
- Acute control of infections with IV antibiotics - neutropenia makes this high risk
- Stem cell transplant
What is chronic myeloid leukaemia? What is its epidemiology? What are the vast majority of cases associated with?
- Proliferation of myeloid blood cells - affects neutrophils, basophils, eosinophils and macrophages
- Seen the most in adults 40-60
- Vast majority associated with the PHILIDELPHIA CHROMOSOME
What are the signs and symptoms of chronic myeloid leukaemia?
- MASSIVE HEPATOSPLENOMEGALY
- GOUT
- Loss of weight, fever, sweats, fatigue
- Bleeding (platelet dysfunction)
- Abdominal pain (splenic enlargement)
- Anaemia - breathlessness, fatigue, pallor
- Infection
What are the investigations for chronic myeloid leukaemia? What would be diagnostic? Which chromosome is seen in 80% of cases?
- FBC - HIGH WBCs, anaemia, raised myeloid cells
- PHILIDELPHIA CHROMOSOME seen in 80+% of cases - t(9;22), stimulates cell division
- Increased B12
- Blood film - left shift (indicates presence of immature neutrophils), basophilia
What is the treatment for chronic myeloid leukaemia?
- Chemotherapy
- TYROSINE KINASE INHIBITORS, e.g. IMATINIB given orally
- Stem cell transplant
(CM went to the PHILIDELPHIA centre and got MASSIVE HEPATOSPLENOMEGALY AND GOUT. She got given TYROSINE KINASE INHIBITORS)
What is chronic lymphoblastic leukaemia? What is its epidemiology?
- Chronic lymphoblastic leukaemia = proliferation of the B lymphocytes
- MOST COMMON LEUKAEMIA IN ADULTS
- Seen in adults 70+
- Immunocompromised people = 3x more likely to develop CLL
- Pneumonia can trigger CLL
What are the signs and symptoms of chronic lymphoblastic leukaemia?
- OFTEN ASYMPTOMATIC
- Lymphadenopathy
- Severe cases see weight loss, sweats and anorexia
What are the complications of chronic lymphoblastic leukaemia?
- Richter’s syndrome = transformation to aggressive lymphoma
- Autoimmune haemolysis
- Bone marrow failure
What are the investigations for chronic lymphoblastic leukaemia? What is diagnostic?
- FBC - high WBC with high lymphocytes
- Blood film - small mature lymphocytes, SMUDGE CELLS (remnants of leukocytes)
How do we treat chronic lymphoblastic leukaemia?
- WATCH AND WAIT in early stages
- Chemotherapy (RITUXIMAB)
- Targeted therapy, e.g. bruton kinase inhibitors (ibrutinib)
Name the 3 broad categories of red cell disorders.
- Haemoglobinopathies
- Membranopathies
- Enzymopathies
What is normal adult haemoglobin made of? What is foetal haemoglobin made of? What is haemoglobin S?
- 2 alpha and 2 beta chains
- 2 alpha and 2 gamma chains
- Haemoglobin S is a variant of Hb arising from a point mutation in the beta globin gene. The mutation leads to a single amino acid change, valine -> glutamine
What is sickle cell disease/anaemia? Is it recessive or dominant, and are the carriers heterozygous or homozygous? What is its epidemiology?
- Sickle cell disease = production of abnormal beta-globin chains via a single base mutation of A to T. HbS polymerises - sickle shaped RBC (reduced carrying capacity for O2)
- Autosomal recessive disorder
- Sickle cell anaemia is homozygous, sickle cell trait is heterozygous
- Most common in Africa
What is the advantage of being a carrier of sickle cell disease?
Carriage offers protection against falciparum malaria
If both parents are carriers of the sickle trait. What is the chance that their first child will have sickle cell disease?
Their offspring have a 1/4 chance of being affected with a sickle cell disease. (50% chance of being a carrier)
How long do sickle cells last for?
5-10 days - this explains why sickle cell disease is described as haemolytic
What are the risk factors for sickle cell anaemia?
- Low O2
- Cold weather
- Parvovirus B19
- Exertion
What are the chronic complications of sickle cell anaemia?
- Avascular necrosis of joints
- Silent CNS infarcts
- Retinopathy
- Nephropathy
- ED
What are is the acute presentation of a crisis for sickle cell anaemia?
- MSK: bone pain, joint pain
- Infection
- Resp: dyspnoea, cough, hypoxia
- CNS: stroke
- GI: sequestration crisis (blood outflow from the spleen is blocked, blood accumulates - splenomegaly)
What are the investigations for sickle cell anaemia? What is diagnostic?
- Blood film - sickled erythrocytes seen
- Blood count - low Hb (range of 60-80 g/L), low MCV
- POSITIVE sickle solubility test - does not distinguish trait from disease SO NOT DIAGNOSTIC
- Haemoglobin electrophoresis - CONFIRMS DIAGNOSIS as detects HbS band
What is the treatment for sickle cell anaemia?
- Acute attacks: IV fluids, morphine, oxygen, blood transfusion
- Chronic: oral HYDROXYCARBAMIDE to reduce frequency of crises, stem cell transplant, folic acid
What is the significance of parvovirus for someone with sickle cell disease?
Parvovirus is a common infection in children. It leads to decreased RBC production and can cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan. This can be dangerous for someone with sickle cell
What is thalassaemia? What are the different types?
- There is reduced synthesis of one or more globin chains leading to a reduction in Hb -> anaemia
- Alpha and beta thalassaemia
What is alpha thalassaemia? What are the different types?
- Gene deletion on one or both of alpha chains (chromosome 16)
- 4 gene deletion (Hydrops foetalis)
- 3 gene deletion (Hb H disease)
- 2 gene deletion (trait)
- 1 gene deletion (silent carrier)
What is the presentation for the different types of alpha thalassaemia?
- Alpha (trait) [-a/-a or –/aa] - asymptomatic or mild anaemia
- Alpha (Hb H disease) [-a/–] - mild microcytic anaemia, haemolytic anaemia
- Alpha (Hydrops foetalis) [–/–] - incompatible with life
What are the investigations for alpha thalassaemia? What is diagnostic?
- FBC showing microcytic anaemia
- Elevated serum iron
- Haemoglobin electrophoresis
Describe the treatment for alpha thalassaemia.
- Treat with transfusions during crises
- Desferrioxamine to aid iron excretion
- Folic acid
What is beta thalassaemia? What are the different types?
- Excess alpha chains, few beta chains. Point mutations in the gene (chromosome 11)
- Minor
- Intermedia
- Major
What are the presentations for the different types of beta thalassaemia?
- Minor (heterozygous) - asymptomatic, hypochromic RBC’s
- Intermedia - anaemia, frequent infections
- Major - failure to thrive, transfusion dependant (signs: bossing of skull, overgrowth of maxilla)
Where would you normally take a bone marrow biopsy from?
Posterior iliac crest
What are the investigations for beta thalassaemia? What is diagnostic?
Blood film - will see reticulocytosis, microcytic anaemia, and nucleated red blood cells in circulation
- Hb electrophoresis
Which clinical classification of thalassaemia relies on regular transfusions?
Thalassaemia major