Haematology 2 Flashcards
What are the three classification systems used for leukaemia?
Morphological
Immunological
Cytogenetic (chromosomal analysis)
What symptoms are seen in ALL and what would you expect the Blood work to show?
Anaemia Bruising/ petechiae Recurrent infections Mediastinal mass Hepatomegaly Splenomegaly Lymphadenopathy Orchidomegaly Cranial nerve palsies
Bloods:
- Anamia
- MVC - normal/ raised
- Leucocyte count can be high or low!
- Thrombocytopenia
- Blood smear - blast cells
Bone marrow
- hypercellular
Special tests:
- LP *all ALL should receive lP
What is the general management for leukemia?
Support
- blood transfusion
- IV fluids
- Allopurinol
Infection control
- neutropenic sepsis
Chemotherapy
- induction
- consolidation
- remission
Allogeneic marrow transplantation
What are some signs of AML?
Anaemia
Bleeding
Infection
DIC
Hepatomegaly Splenomegaly Gum hypertrophy Skin involvement CNS involvement
Diagnosis:
- WCC is usually high but may be low
- Bone marrow biopsy - blast cells
Auer rods differentiate from ALL
What are the complications of bone marrow transplant?
GVHD
Opportunistic infection
Relapse
Infertility
What is the management of CLL?
If symptomatic:
- chemotherapy
- Radiotherapy (helps lymphadenopathy and splenomegaly)
- Stem cell transplant
- Supportive care
1/3 never progress
1/3 progress slowly
1/3 develop richters lymphoma
Who gets hodgkin’s lymphoma?
Bimodal
- young adults 15-24
- elderly
SLE patients
Post transplantation
What are the symptoms of hodgkin’s lymphoma?
Enlarged rubbery lymph node - changes in size Fever Weight loss Night sweats Pruritus
Splenomegaly
anaemia
Cachexia
Hepatomegaly
What investigations should be done into hodgkin’s lymphoma?
Bloods:
- FBC - low lymphocytes is poor sign
- Blood film
- ESR
- LFTs - infiltration/ obstruction due to nodes
- LDH - high during turnover
- Urate levels - high during turnover
- U&Es - to ensure normal function prior to treatment
X-ray:
- CXR - for mediastinal mass
- CT Chest/ Abdo/ Pelvis
- PET SCAN
- ECHO - this is because some of the treatment is going to require good cardiovascular function.
What is meant by stage 1A or 1B or 2B etc in lymphoma?
Number refers to the Ann arbor classification
Letter refers to absence or presence of B symptoms.
A - asymptomatic
B - symptoms, night sweats, weight loss etc.
What is the treatment of Hodgkin lymphoma?
Stages 1-2A
- Radiotherapy + short chemotherapy course
> 2A
- ABVD chemotherapy courses
What are the complications of Hodgkin’s lymphoma treatment?
Risk of secondary malignancies
- breast
- lung
- melanoma
- thyroid cancers
Ischemic heart disease
- radiation
Infertility
What are the risk factors for Non - hodgkin lymphomas?
Immunodeficiency
- Drugs
- HIV
Infections:
- EBV
- H. Pylori
Autoimmune conditions:
- Sjogrens
- SLE
Drugs:
- Ciclosporin
- Radiation therapy
What are the signs and symptoms of non-hodgkin lymphoma?
Superficial lymphadenopathy This can cause compression of surrounding structures: - Biliary obstruction - ureteric obstruction - nerve compression - dysphagia
Symptoms due to local inflammation:
- Ascites
- Pleural effusion
B symptoms
Pancytopenia
- infection
- anaemia
Extranodal disease:
- Gut
- MALT - H.Pylori related - symptoms of gastric Ca
- Non - MALT - Symptoms of gastric Ca
- Enteropathy related T cell lymphoma - Skin
- Mycosis Fungoides - Oropharynx
- Waldeyer’s ring
Systemic features:
- weight loss
- night sweats
- fever
- Pancytopenia
What investigations should be done into Non - Hodgkin’s lymphoma?
Much of the tests for Non-hodgkin’s are the same as hodgkin’s, expect there are few others:
Bloods:
- FBC
- U&Es
- LFTs
- LDHs
*HIV testing
Node biopsy
Marrow aspiration + Trephine
Immunophenotyping
LP
- if CNS signs
CT Chest/ Abdo/ Pelvis
What is the management of Non- Hodgkin lymphomas?
Low grade:
- no treatment if asymptomatic
- Radiotherapy
- Rituximab
High Grade:
- RCHOP
Prior to taking bone marrow aspiration what may need to be done?
Coagulation disorders may need to be corrected.
What are the possible causes for pancytopenia?
Bone marrow failure:
- aplastic anaemia
- Viral - Parvovirus B19
Bone marrow infiltration:
- Leukaemia
- Myeloma
- Lymphoma (NHL)
- Myelodysplasia
Infective Haematopoiesis:
- B12 deficiency
- AIDS
Peripheral pooling:
- Myelofibrosis
- SLE
- Hypersplenism
What diagnostic test is required in Pancytopenia?
Bone marrow aspiration
+
Marrow Trephine
- posterior iliac crest
How should pancytopenia be investigated?
Look for underlying causes.
Bloods:
- FBC
- Blood film
- B12/ Folate
Bone marrow aspiration and trephine
How is pancytopenia managed?
Address underlying cause
Blood products
Platelets
Neutropenia control
What are infections that can be transfused via blood transfusion:
Hep C
Hep B
HIV
vCJV
Which factors help to discriminate between High grade and low grade lymphomas?
High grades:
- Diffuse large B cell
- Burkitt’s
- Mantle
Fast growing
More active B symptoms
Higher levels of LDH
CRP is high
What are the complications of CLL?
Autoimmune Haemolytica
Agammaglobulinemia
What are some differentials to Non- hodgkin lymphoma?
Other leukaemias
Sarcoidosis
EBV
Who should undergo further investigations for DVTs?
> 55 years which was unprovoked
those with multiple DVTs
What are some of the clinic signs of myelofibrosis?
What investigations?
What is the treatment?
Recurrent DVTs in unusual places
Episodes of gout - High urate turnover
High platelet count on FBC
Bone marrow biopsy with trephine needed for diagnosis
- fibrosis within the bone marrow
Treatment:
- supportive
- Bone marrow transplant
How does Essential thrombocythemia present?
how is it treated?
Abnormal clotting
Abnormal bleeding
Microvascular occlusion
Investigations:
- FBC - thrombocytosis
- rule out other causes of thrombocytosis
Treatment:
- Aspirin
- Hydroxycarbamide
If there is signs of haemolytic anaemias, what further investigations should be done in the blood work up?
LDH
Haptoglobin
LFTs - bilirubin
If haemolysis is proven then:
Direct Coombs test should be performed.
What advice should be given to those with G6PD? and how is it transferred?
x-linked
mainly:
- mediatrian
- African
Avoid:
- Henna tattoos
- Antimalarials - Primaquine
How is hereditary spherocytosis and elliptocytosis passed on and how are the treated?
Autosomal dominant
Treated with splenectomy
As well as looking investigating the blood work up, what else should be investigated in beta thalassemia?
MRI of heart
- iron build up
TFTs
- thyroid toxicity to iron build up
Pancreas dysfunction
- same reason
What are some of the complications of beta thalassemia outwith Anaemia and extramedullary hematopoiesis?
Hypogonadism
Hypothyroidism
Pancreatic dysfunction
Heart disease
Hypocalcaemia
Which group of people are most likely to get Beta thalassaemia?
Mediatrerian
Far East
How is Beta thalassaemia managed?
- Folate supplements
- Regular blood transfusions
- Iron Chelating agents
- Splenectomy
- Hormone replacement - due to secondary damage
- Bone marrow transplant - in the young
Prevention:
- antenatal diagnosis - fetal blood or DNA
What are the signs and symptoms of polycythemia ruba vera? How is it investigated and diagnosed?
>60 year olds Hyperviscosity symptoms: - headache - amourosis fugax - lethargy - visual changes "looking through watery car windscreen"
tinnitus
Itch after warm bath
Facial Plethora
Investigations:
- FBC
- Haematinics
- B12 - increased
Bone marrow aspiration
- hypercellular with erythroid hyperplasia
- EPO levels (low)
- JAK2 investigations
Treatment:
- Aspirin
- Venesection
- Hydroxycarbamide
In Beta thalassemia what would you see on electrophoresis of the serum?
Increased HbF
Increased HbA2
Lack of HbA
Name some differentials for Hodgkin’s lymphoma:
- CLL
- Abscess from infection
- Metastasis from oesophagus
- Non- Hodgkin’s lymphoma
Lipoma
What is another type of NHL which affects the gastrointestinal tract?
MALT
- associated with H.Pylori
Treated with:
- antibiotics - remove source
- Chemotherapy
- radiotherapy
What are the causes of Burkitt’s lymphoma?
Endemic - EBV
HIV related
Sporadic - most likely to affect ileocaecal valve
How can fibrogen be measured?
Thrombin time
What will the PaO2 be in anaemia?
Normal, PaO2 is the diffusion of O2 in blood
What is the MCH?
Mean corpuscle Haemoglobin
- will be low in Anemia
What are the typical x-ray appearances seen on beta thalassemia?
Hair on end appearance of skull
Bossing of the skull
Thinning of the cortical bone
What is the reticulocyte count in iron deficiency anemia?
Low
- not enough iron to create enough RBCs
What is the mutation defect in sickle cell?
Non conservative point mutation.
glutamine to valine
Making the beta chain non water soluble.
What are some triggers to cause a sickle cell to sickle?
Low oxygen
Infection
Acidosis
Dehydration
What are the crisis that occur in sickle cell disease?
Aplastic crisis
Splenic sequestration
Acute chest syndrome
If someone has a prolonged APTT what test should be done next?
Corrected APTT
How is haemophilia A and B inherited?
X linked recessive
What are the INR levels wanted for various conditions of warfarin?
P.E
Post DVT
AF
= 2.5
Mechanical heart valve
antiphospholipid syndrome
coronary artery bypass
= 3.5
What management should be given in a major bleed with increased INR?
Stop warfarin
Give vitamin K
FFP
+/-
Prothrombin complex concentrate
What are the different types of von willebrand disease?
Type 1: Quantitative deficiency
Type 2: Qualitative deficiency
Type 3: Complete lack of Von Willebrand
- inherited recessively
What are some causes of thrombocytosis?
Splenectomy
Malignant disease
Post surgery
Post bleeding
- afterwards
Acute phase reactant - so anything that stimulates
Iron deficiency
What would cause a raised thrombin time?
Fibrinogen deficiency
Heparin
What is needed for there to be a graft vs host disease?
- Graft tissue must contain immune cells
- Host must be immune suppressed
- The host must be immunologically different
What are the symptoms of GVHD? and the order in which they occur
1st Skin
- painful itchy rash
- lacrimal glands
2nd Liver
- Jaundice
- Raise in LFTs
G.I
- diarrhoea
- Intestinal disease
What can help differentiate between the microcytic anaemias?
Serum Iron TIBC Serum ferritin Iron in marrow Distribution of width **Only deficiencies will cause this
Mentzer test** for IDA vs Thalassemia
*thalassaemias tend to have normal levels across all
What is the test that can be done into pernicious anaemia?
Schilling test
- radioactive B12 is given
Urine is collected. Normally 10% is excreted. if this is abnormal then oral intrinsic factor is given. and the above is repeated.
- if normal excretion then diagnosis of pernicious anaemia
List some cause so folate deficiency:
Diet Alcohol Coeliac disease Antifolate drugs - methotrexate Inflammatory bowel disease
What is the two types of electrophresis done on multiple myeloma and how do they differ?
Plasma electrophoresis - shows there is a spike
Immunoelectrophoresis - differentiates the spike
How does myeloma cause kidney failure?
Amyloidosis build up
Renal tubular obstruction
- due to bence Jone’s proteins
Excessive use of NSAIDs due to bone pain
Direct toxicity of the paraproteins
Whats the pneumonic for Myeloma?
CRABBI
- calcium
- Renal
- Anaemia
- Bone pain
- Bleeding
- Infection
What is a poor prognostic factor in myeloma?
Low Albumin
What is the colour of urine in pre-hepatic jaundice?
Coco cola like urine
How is G6PD deficiency inherited and thus who won’t pass it on?
X - linked. therefore if father has it - they won’t pass it on.
Break down of the platelet bleeding disorders
Idiopathic thrombocytopaenic purpura (ITP) - Isolated thrombocytopaenia in a relatively well person
Thrombotoic thrombocytopaenic purpura (TTP) - Thrombocytopaenia in a very unwell person
Haemolytic uraemic syndrome (HUS) - Thrombocytopaenia, schistocytes, renal failure, post-dysentry
Henoch Schonlein Purpura (HSP) - Abdo pain, joint pain, haematuria, purpura. Kids.
Haemorrhagic Haemolytic Telangiectasis (HHT) - Epistaxis, GI bleeds, telangiectasia
How should tranexamic acid be administered in a major bleed?
IV slow injection
What type of transplant is giving to those with lymphoma?
Autologous Stem cell transplant
- use of GSF to draw out stem cells which can be collected and re-introduced following chemotherapy to shut down the patients bone marrow
When carrying out cytogenetic testing on leukemia, what type of molecular testing can be done?
FISH
When planning therapy for lymphoma/ leukemia etc what tests should be done?
Biochemistry
- U&Es etc
Cardiac function
- ECG
- Echocardiogram
What are the classic signs of Iron deficiency anaemia?
Fatigue Breathlessness Headaches Tinnitus Palpitation
Signs:
- Pallor
- Hyperdynamic circulation
- Flow murmur
- Koilonychia
- Esophageal webs
- Angular stomatitis
Why do you get a lemon tinge in B12 deficiency?
Hypercellularity with breakdown in the marrow
- haemolytic anaemia
What test is used to diagnose Hereditary spherocytosis? and what is the treatment?
Osmotic fragility test
Splenectomy and folate
What is the long term management of sickle cell?
Penicillin V
Pneumococcal vaccine
Folate
Hydroxycarbamide
Bone marrow transplant - controversial
Treatment for haemophilia A:
Desmopressin
Recombinant factor 8
- for severe.
- Can be reduced by autoantibodies against it
Tranexamic acid if severe bleeding
What are the clinical signs of antiphospholipid syndrome?
CLOT
- Coagulation defect - Increased APTT
- Livedo reticularis
- Obstetric complications
- Thrombocytopenia
What investigations should be done into suspected thrombophilia?
What is the treatment?
FBC Coagulation studies Factor V leiden Anti-cardiolipin/ Lupus Anticoagulant test Immunoassays for Protein C and S PCR for thrombin gene defect
Life long anticoagulation
- warfarin
What is the staging for CLL?
Binet staging
What are the major symptom of bone marrow failure and what treatment can be used in primary causes?
Major symptoms are all those in keeping with pancytopenia but bruising and bleeding are big problems.
- young person
- Bone marrow transplant
- > 40
- Anti - thymocyte globulin (anti T cell globulin to prevent more destruction in the bone marrow)
- ciclosporin
What are the most common thrombophilia diseases:
Factor V leiden
- APC resistance
Prothrombin gene mutation
- higher levels of prothrombin
Protein S and Protein C deficiency
Antithrombin III deficiency
Acquired
- phospholipid syndrome
Name some drugs that can cause bone marrow suppression:
Sulfonamides
Chloramphenicol
Carbimazole
Chemotherapy
Phenytoin
What is the immunosuppressive drugs used in treatment of bone marrow failure?
Anti - thymocyte globulin
Ciclosporin
What is it called when there is painful extremities associated with polycythemia vera?
Erythromelalgia
- due to abnormal dilation of vessels
What would you expect to see on urine dipstick of someone with myeloma?
Increased specific gravity
- bence jones proteins don’t show up
What are some of the complications of myeloma?
Hypercalcemia
Cord Compression
AKI
Hyperviscosity
- may require plasmapheresis
What are the poor prognostic indicators in myeloma?
Low albumin
Beta 2 microglobulins
What defines monoclonal gammopathy of uncertain significance?
<30g/L of paraprotein
<10% blast cell
Lack of CRAB symptoms
What is Waldenstrom’s macroglobulinemia defined by:
IgM
- only agglutinates when cold
Peripheral neuropathy symptoms
What are some complications of splenectomy?
Super infection
Early retribution of platelets - VTE
Left lower lobe atelectasis
List some causes of very high ESR:
Myeloma SLE AAA Prostate cancer Ulcerative colitis
What are some causes of Basophilia:
CML
Parasitic infection
What are some raised lab features associated with Pernicious anemia?
Increased homocysteine
Increased gastrin levels
Achlorhydria
Compare and contrast macrocytic anaemia vs megaloblastic anemia:
Megaloblastic:
- Hypersegmented neutrophils
- Neurological deficits
- Pancytopenia
- Enlarged glossitis
*macrocytic anaemia does not have these
Why might there be a high level of haptoglobin? making it difficulty to interrupt results?
Haptoglobin is an acute phase reactant protein
- thus may raise inflammation and mask the true effects of the haemolysis
List some complications of sickle cell:
Acute chest syndrome
Sequestration crisis
Aplastic crisis
Priapism
Ulceration
Kidney damage
- haematuria can be seen
Gallstone formation
What investigations should be done into haemolytic anaemia?
FBC Blood film LDH Haptoglobin Reticulocyte count Hemoglobin level Plasma electrophoresis - sickle cell
Orifices:
- urine analysis
Special tests:
- Coomb’s test
What are some differentials for Myeloma?
MGUS
Amyloidosis
Waldenstrom’s macroglobulinemia
Lymphoma
What is the mechanisms of Leiden V mutation?
Factor V resistant against protein C
In renal failure what is a good anti-thrombin medication to be put on?
Apixaban
What are the mechanisms that lead to kidney damage in myeloma? ad how does it present?
Bence Jones accumulation
- direct toxicity
- accumulation within renal tubules
NSAID use
Amyloidosis
Stones.
Renal failure
Casts
Pyelonephritis
