Haematology Flashcards
Haemophilia A + B have which inheritance pattern?
X-linked recessive
Is haemophilia A or B more common?
A
Haemophilia A is a deficiency of which clotting factor?
Factor 8
Haemophilia B is a deficiency of which clotting factor?
Factor 9
How is mild haemophilia defined
Haematomas following severe trauma
How is moderate haemophilia defined
Haematomas following mild trauma
How is severe haemophilia defined
Spontaneous haematomas
Haemophilia causes ? PT and ? APTT
Normal PT
Prolonged APTT
What special test can you do with blood to confirm a diagnosis of haemophilia?
Mixing study
Mixing patients blood with external plasma will correct the APTT
Besides replacing factor 8, what else can be used to treat haemophilia A?
Desmopressin (vasopressin triggers the release of factor VIII from endothelial cells)
What is the most common inherited bleeding disorder?
Von Willebrand Disease
In VWD what happens to bleeding time, PT and APTT?
Bleeding time increased
PT normal
APTT sometimes normal, sometimes raised
VWD causes high/low factor 8 levels?
Low
Factor VIII levels are a good assessment for vWD because this factor is found bound to vWF in blood, in which state it is protected from rapid breakdown
How do you manage VWD?
Recombinant VWF
Desmopressin (stimulated VWF release from endothelial cells)
Factor 8 concentrate
Which type of VWD won’t respond to Desmopressin?
Type 3
What is the inheritance pattern for type 1 VDW?
Autosomal dominant
What is the inheritance pattern for type 2 VWD?
Autosomal dominant
What is the inheritance pattern for type 3 VWD?
Autosomal recessive
How is type 1 VWD described?
A quantitative deficiency of VWF
How is type 2 VWD described?
A qualitative defect in VWF
How is type 3 VWD described?
Complete absence of VWF
What are the two main types of acute leukaemia?
Acute lymphocytic leukaemia
Acute myeloid leukaemia
Does ALL more commonly affect children or adults?
Children
Does AML more commonly affect children or adults?
Adults
Which cells develop from the lymphocytic cell line?
Natural killer cells
B cells –> plasma cells
T cells
Which cells develop from the myeloid cell line?
Basophils
Eosinophils
Neutrophils
Describe the pathophysiology of acute leukaemia
Acquired gene mutations affect how bone marrow cells divide and mature
Either lymphoid/myeloid stem cells proliferate but differentiation/maturation stops in the early stages
This results in accumulation of abnormal and dysfunctional blasts
This disrupts normal haematopoiesis –> leukopenia, thrombocytopenia, anaemia
Abnormal cells also infiltrate organs such as liver, spleen, nodes, skin
Risk factors for ALL
Risk factors = often none, HTLV (Human T-cell lymphotropic virus), Down syndrome, neurofibromatosis type 1, ataxia telangiectasia
Risk factors for AML
Risk factors = pre-existing haematopoietic disorder (myelodysplastic syndromes, aplastic anaemia, myeloproliferative disorders), previous chemotherapy or radiation, smoking, benzene exposure, Down syndrome, Fanconi anaemia
Clinical features of acute leukaemia
Sudden onset, rapid progression over days/weeks
Fatigue, pallor, weakness
Bleeding, petechiae, purpura
Frequent infections, fever
Features that are more common/specific to AML rather than ALL
Leukaemia cutis/myeloid sarcoma (blue/puruple/grey nodular skin lesions)
Gingival hyperplasia
Extremely high WBC counts that can cause leukostasis
Features that are more common/specific to ALL rather than AML
Fever and constitutional sx Lymphadenopathy Hepatosplenomegaly Bone pain Mediastinal involvement CNS involvement
Are Auer rods seen in ALL or AML
AML
What is ‘leukaemic hiatus’ on blood film?
A way to differentiate AML from CML
In CML myeloid cells of all stages are present whereas in AML its mainly blasts and mature (no in-between).
What are the nuclei of lymphoblasts like in ALL
Large and irregular
What are the nuclei of myeloblasts like in AML
Round or kidney shape
Is myeloperoxidase positive or negative in ALL and AML
Negative in ALL
Positive in AML
What symptoms/problems can leukostasis cause?
Chest pain, headache, altered mental status, priapism, DIC
What is tumour lysis syndrome?
Rapid destruction of tumour cells causing a massive release of intracellular components –> renal damage
What happens to K, Ca, PO4 and urea in tumour lysis syndrome?
High K
High PO4
Low Ca
High urea
What are some clinical features of tumour lysis syndrome?
Nausea, vomiting, diarrhoea, lethargy, haematuria, seizures, arrhythmias, tetany, muscle cramps, paraesthesia
What is the basic pathological difference between acute and chronic leukaemia?
In acute leukaemia cells dont mature
In chronic leukaemia cells don’t work effectively (CLL cells dont die as they should, CML cells divide too quickly)
What are the two main types of chronic leukaemia?
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia
Who tends to be affected by CLL?
Elderly men
What are some clinical features of CLL?
Constitutional/B symptoms Painless lymphadenopathy Recurrent infections Sx of anaemia Sx of thrombocytopenia Chronic pruritus/urticaria Hepatomegaly/splenomegaly
What would an FBC show in CLL?
Persistent lymphocytosis with high percentage of small mature lymphocytes
Granulocytopenia
Anaemia
Thrombocytopenia
What does blood film show in CLL?
Smudge cells (Gumprecht shadows)
Is CLL a low or high grade malignancy?
Low grade
What is Richter’s transformation/syndrome?
Transformation of CLL into a high grade NHL
How can Richter’s transformation/syndrome present?
Rapidly progressive lymphadenopathy
New onset of B symptoms
High LDH
What are the three distinct clinical phases of CML?
Chronic
Accelerated
Terminal/Blast crisis
Describe the chronic phase of CML
The chronic phase is characterized by nonspecific symptoms (fever, weight loss, night sweats) and splenomegaly and can persist for up to 10 years
Describe the accelerated phase of CML
The accelerated phase is characterized by complications secondary to the suppression of the other cell lines (thrombocytopenia, anemia, neutropenia, recurrent infections, leukostasis). Develop extreme splenomegaly in accelerated phase and this is often a sign of transition to terminal phase.
Describe the terminal phase/blast crisis of CML
The clinical picture of the terminal phase, blast crisis, resembles that of acute leukemia. Rapid progression of bone marrow failure causes pancytopenia and bone pain Blast crisis (progression of CML to AML) occurs when increased division of myeloid cells in CML leads to increased mutations resulting in totally immature cells being produced (AML).
Is hepatosplenomegaly more common in CML or CLL?
CML
What drug is really good at treating CML?
Imatinib (tyrosine kinase inhibitor)
What would FBC show in CML?
Extrememe leukocytosis
Basophilia
Thrombocytosis
What is lymphoma
A type of blood cancer that causes tumours to form in lymph nodes
What are the two broad types of Hodgkin lymphoma
Classical
Nodular lymphocyte predominant
What are the four types of classical Hodgkin lymphoma?
Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
Where does nodular sclerosing classical hodgkin lymphoma most commonly localise?
Mediastinal and cervical lymph nodes
Where does mixed cellularity classical hodgkin lymphoma most commonly localise?
Abdominal and splenic lymph nodes
Where does lymphocyte rich classical hodgkin lymphoma most commonly localise?
Cervical and axillary nodes
What are some risk factors for developing hodgkin lymphoma?
EBV mononucleosis
Immunodeficiency - HIV, meds, chemo
Autoimmune diseases
Clinical features of hodgkin lymphoma
Painless lymphadenopathy Sx of mediastinal mass (chest pain, SOB) B symptoms Hepatosplenomegaly Pel-Ebstein fever (temp for 1-2 weeks, normal for 1-2 weeks) Alcohol induced pain Pruritus
Reed-Sternberg cells are pathognomic for X?
Hodgkin Lymphoma
What is the name of the classification system for Hodgkin lymphoma?
Ann-Arbor classification
Describe the Ann-Arbor classification for HL
I. 1 lymph node area
II. 2+ but confined to one side of the diaphragm
III. 2+ on both sides of the diaphragm
IV. Disseminated spread into an extralymphatic organ. IVA if asymptomatic, IVB if B symptoms, IVX if bulky disease
Which chemo regimen is typically used for HL
ABVD - adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine)
Is HL or NHL more common?
NHL
How are non-hodgkin lymphomas categorised?
B cell or T cell
High grade or low grade
Are B-cell or T-cell NHL more common?
B cell
What are the low grade B-cell non-hodgkin lymphomas?
Chronic lymphocytic leukaemia Hairy cell leukaemia Waldenstroms macroglobulinaemia Follicular lymphoma MALT lymphoma
What is the most common low-grade non-hodgkin lymphoma?
Follicular lymphoma
What are the high-grade non-hodgkin lymphomas?
Burkitt lymphoma
Diffuse large B cell lymphoma
Precursor B cell lymphoblastic lymphoma
Mantle cell lymphoma
What is the most common NHL in adults?
Diffuse large B cell lymphoma
What is the low grade T cell NHL?
Mycosis fungoides (cutaneous lymphoma)
What are the high grade T cell NHLs?
Adult T cell lymphoma
Cutaneous T cell lymphoma
Precursor T cell lymphoblastic lymphoma
What are the risk factors for developing NHL
Chromosomal translocations EBV HIV HTL HCV H.pylori (MALT) Autoimmune disease Immunodeficiency Benzene exposure Radiation
Clinical features of NHL
Painless lymphadenopathy (insidious onset in low grade, generalised in high grade) Splenomegaly Hepatomegaly GI/skin/thyroid/CNS involvement B symptoms Fatigue/weakness Anaemia Bleeding Infections
FBC findings in NHL
Anaemia
High/low WBC
Thrombocytopenia
High LDH
All NHL is treated with a curative approach apart from which category?
Advanced low-grade
Multiple myeloma is a malignant disease causing uncontrolled proliferation of which type of cell?
Plasma cells
Clinical findings of multiple myeloma
Bone pain (back, spontaneous fractures) Sx of hypercalcaemia B symptoms Weakness and anaemia Recurrent infection Petechial bleeding Foamy urine (caused by Bence Jones proteinuria)
Blood test findings in multiple myeloma
Anaemia Thrombocytopenia Leukopenia Low reticulocyte count Raised ESR High Ca High creatinine High total protein levels Raised beta-2-microglobulin
Diagnostic criteria for multiple myeloma
Marrow biopsy showing >10% monoclonal plasma cells plus one of: Hypercalcaemia Renal insufficiency Anaemia Bone lesions >60% monoclonal plasma cells in marrow
What is TTP?
Thrombotic thrombocytopenic purpura
A thrombotic microangiopathy
Who typically gets affected by TTP?
Previously healthy adults
What caused TTP?
Acquired autoantibodies that result in accumulation of von Willebrand factor
What are the 5 key clinical findings in TTP?
- Fever
- Neurological signs/symptoms
- Thrombocytopenia
- Haemolytic anaemia
- Impaired renal function
How do you manage TTP
Treat without waiting to confirm diagnosis
Fluid status, electrolytes, acid base
Plasma exchange/FFP
Prednisolone
Who is typically affected by HUS?
Children <5 after 5-10 days of diarrhoea (usually bloody)
What is HUS?
Haemolytic uraemia syndrome
A thrombotic microangiopathy
What causes HUS?
Usually secondary to E.coli 0157:H7 producing shiga-like toxin
What are the 3 key clinical findings of HUS?
- Thrombocytopenia
- Haemolytic anaemia
- Renal insufficiency
What is the management for HUS?
Treat without waiting to confirm diagnosis
Avoid antibiotics and anti-motility agents
Fluid status
Electrolytes
Acid-base balance
BP
When should you suspect ITP?
Isolated thrombocytopenia
Who gets affected by ITP?
Children after a viral illness (acute ITP)
Women of childbearing age (chronic, insidious onset)
What is the management of ITP?
Usually just watch and wait - spontaneously resolves within 6 months for most children
In adults, if platelet count is <30,000 can give corticosteroids
Causes of microcytic anaemia
IDA (late phase) Chronic disease (late phase) Sideroblastic anaemia Lead poisoning Thalassaemia
What does blood film show in sideroblastic anaemia?
Basophilic stippling
Ringed sideoblasts
Causes of normocytic anaemia
Sickle cell disease Pyruvate kinase/G6PD deficiency Hereditary spherocytosis Autoimmune haemolytic anaemia Microangiopathic haemolytic anaemia (TTP, HUS) Blood loss Aplastic anaemia CKD IDA (early phase) Chronic disease (early phase)
Causes of megaloblastic macrocytic anaemia
Vitamin B12 deficiency
Folate deficiency
Medication - Phenytoin, trimethoprin, hydroxyurea, MTX
Fanconi anaemia
Causes of non-megaloblastic macrocytic anaemia
Liver disease Myelodysplastic syndrome Diamond Blackfan anaemia Hypothyroidism Multiple myeloma
How can you differentiate megaloblastic and non-megaloblastic anaemia on blood film?
Megaloblastic has hypersegmented neutrophils, non-megaloblastic doesn’t
What can be used to reverse the effects of unfractionated heparin?
Protamine sulphate
How long does Warfarin take to reach therapeutic range?
48-72 hours
What is Virchow’s triad?
Virchows triad = the three main pathophysiological components of thrombus formation
- Hypercoagulability – increased platelet adhesion, increased clotting tendency (thrombophilia)
- Endothelial damage – inflammatory, traumatic
- Venous stasis – varicose veins, immobilisation, local heat application
Risk factors for DVT
History of VTE Immobilisation Age >60 Malignancy Hereditary thrombophilia (Factor V Leiden) Pregnancy Estrogen use Obesity Smoking
Clinical features of DVT
Unilateral
Swelling
Heavy/tight feeling
Progressive tenderness/dull pain - worse when walking, better when leg elevated
Homan sign (pain on ankle dorsiflexion)
Superficial vein distention
Calf circumference >3cm difference (mark 10cm from tibial tuberosity)
DVT differentials
Post-traumatic swelling Haematoma Lymphoedema Venous insufficiency Ruptured popliteal cyst Cellulitis Compartment syndrome
How id D-dimer used in the assessment of VTE?
Used to rule it out if Wells score is low probability
What is the minimum length of anticoagulation prophylaxis after VTE?
3 months
Clinical features of PE
Acute onset Dyspnea Tachypnea Sudden onset pleuritic chest pain Cough Haemoptysis Tachycardia +/- hypotension JVP distention Co-existing DVT
What may an ABG show in PE?
Respiratory alkalosis with hypocapnia
What is a massive PE?
A large clot which affects perfusion of the right side of the heart
A Wells score of ? makes DVT likely
2 or more
A Wells score of ? makes PE likely?
More than 4
Which coagulation pathway does PT measure?
Extrinsic
Which coagulation pathway does APTT measure?
Intrinsic
What can we used to measure the common coagulation pathway?
Fibrinogen
TT, PT and APTT all affected
What can cause a prolonged PT
Warfarin Factor 7 deficiency Factor 2 deficiency Factor 5 deficiency Factor 10 deficiency
What can cause a prolonged APTT
Heparin Factor 8 deficiency Factor 9 deficiency Von Willebrands Disease Factor 11 deficiency Factor 12 deficiency (but no bleeding)
Mouth slits on RBCs on a blood film indicates what disease?
Hereditary stomatocytosis
What kind of cells are seen on blood film in G6PD deficiency?
Bite cells
What kind of cells are seen on blood film in pyruvate kinase deficiency?
Sputnik cells with protruding spikes
What is the inheritance pattern for thalassaemia?
Autosomal recessive
What is splenic sequestration crisis in sickle cell disease?
Occlusion of splenic artery causes blood to pool and get trapped in the spleen causing LUQ pain, anaemia, reticulocytosis and hypotension
What causes aplastic crisis in sickle cell disease?
Parvovirus B19 infection
Which medication can be used to try and prevent sickle cell crisis?
Hydroxyurea
What can trigger sickle cell crisis?
Reduced oxygen tension/hypoxia Dehydration Stress Infection Pregnancy Acidosis
How do you manage acute sickle cell crisis?
Hydration Analgesia Nasal oxygen VTE prophylaxis Bed rest Exchange transfusions if severe
Difference in blood test results between Von Willebrands disease and Haemophilia A
Both with have prolonged APTT
VWD will have prolonged bleeding time
HA will have normal bleeding time
