Hematology Flashcards
Risk factors for VTE
Age >60 Surgery >30 mins Immobilisation Trauma Obesity COCP previous VTE Congenital / acquired hypercoagulable states Pregnancy HF Malignancy
Management of urticarial reaction to a blood transfusion
Slow / temporarily stop blood transfusion
IV / oral chlorphenamine
Symptoms of haemolytic transfusion reaction
Burning at infusion site Headache Nausea Chills Fever Chest tightness
In what condition howel jolly-bodies occur?
Hyposplenism
When do Burr cells occur?
Uraemia
When do Heinz bodies occur?
Glucose-6-phosphate dehydrogenase deficiency
When may reticulocytosis occur?
Bleeding, haemolysis
When may target cells occur?
Liver disease,
Iron deficiency anaemia
What causes macrocytic anaemia with glossitis and peripheral neuropathy?
B12 deficiency
What drugs may cause folate deficiency?
Phenytoin Trimethoprim Methotrexate Sulfasalazine Oral contraceptive pill
Causes of a macrocytic anaemia?
B12deficiency, folate deficiency, hypothyroidism Alcohol excess Reticulocytosis Multiple myeloma Myeloproliferative disorders Aplastic anaemia
Causes of a Microcytic anaemia?
Iron deficiency
Thalassaemia
Sideroblastic anaemia
Causes of a Normocytic anaemia?
Chronic disease (E.g. malignancy, rheumatoid arthritis)
Haemolytic anaemia
Acute blood loss
Marrow infiltration
Signs and symptoms of sickle-cell anaemia?
Anaemia Shortness of breath Dizziness Headaches Cold hands and feet Pain Splenic crisis Infections Priapism Stroke Gallstones Leg ulcers
What causes dark urine in the morning and a positive hams test?
Paroxysmal nocturnal haemalobinuria
Weightloss plus anaemia and dysphagia suggests what ?
Oesophageal carcinoma
Weightloss plus anaemia and painless obstructive jaundice suggests what ?
Carcinoma of the head of the pancreas
In what condition do reed Sternberg cells occur?
Hodgkin’s lymphoma
In what condition do auer Rods occur?
Acute myeloid leukaemia
In what condition does the Philadelphia chromosome occur?
Chronic myeloid leukaemia
Features of myeloma?
Bone pain Fractures Nerve compression Hypercalcaemia Bone marrow failure --> Anaemia, Clotting problem, Infection Hyperviscosity --> retinal haemorrhage Renal failure
What is myeloma?
malignant proliferation of plasma cells
Leading to bone marrow infiltration and bone destruction and bone marrow failure
Causes of pancytopenia
Aplastic anaemia,
Bone tumours,
hypersplenism,
sepsis,
Causes of excess erythropoietin?
Polycystic kidney disease Renal cell carcinoma, adrenal tumour, hepatocellular carcinoma Cerebellar haemangioblastoma
Common symptoms of antiphospholipid syndrome
DVT Stroke Multiple miscarriage Placental infarction Migraine Livedo reticularis
Syx of anaemia
Fatigue Dizziness Palpitations Pallor Cold skin SOB Muscle weakness
Signs of anaemia
Low BP
Tachycardia
Splenomegally
Pallor
What is thrombopoiesis
Platelet formation in the bone marrow
Formed from megakaryocytes
When are basophils raised
Allergy
Parasitic infection
When are eosinophils raised
Allergy
When are neutrophils raised
Acute inflammation
What are the primary lymphoid tissues?
Bone marrow
Thymus
What are the secondary lymphoid tissues
Lymph nodes
Spleen
Mucosal associated lymphoid tissue
What is phlebitis
Inflammation of a vein
What is thrombophlebitis
Inflammation of a vein associated with a clot
Risk factors for peripheral vascular disease
Male History CVD Increased age Family history DM Hypercholesterolaemia Hypertension
Symptoms of idiopathic thrombocytopenia purpura
Easy bruising
Mucosal bleeding
Menorrhagia
Epistaxis
Features of thrombotic thrombocytopenic purpura (TTP)
Thrombocytopenia Microangiopathic haemolytic anaemia Neurological signs Renal impairment Fever
Features of hereditary haemorrhagic telangiectasia (HHT)
Telangiectasias On skin, lips and mucosal surfaces
Small aneurysms on fingertips, face, nasal passage, tongue, lung, GIT.
AV malformations
Recurrent bleeding (E.g. Epistaxis)
Causes of thrombocytopenia
Leukaemia myeloma bone marrow cancer myelofibrosis B12 deficiency folate deficiency Marrow hypoplasia DIC ITP TTP EBV Gram negative septicaemia Hypersplenism Liver disease SLE
What is the most common congenital bleeding disorder?
Haemophilia A
What is the inheritance of haemophilia A?
X linked recessive
Features of haemophilia A?
Bruising
Excess bleeding
Spontaneous haemarthrosis
Muscle haematoma
What is Christmas disease?
Haemophilia B
What is von Willebrand disease.
Common Mild Bleeding disorder Autosomal dominant Onset in adolescence
Features of von Willebrand disease
Bruising epistaxis menorrhagia GI haemorrhage gum bleeding
What may initiate DIC?
Infections
Cancers
Obstetric complications
Signs of DIC
Acutely ill patient
Shock
Bruising, purpura
Initial thrombosis then bleeding e.g From mouth,nose, vene puncture sites
Prolonged PT, APTT, TT
Low fibrinogen
End organ ischaemia –> Multiorgan failure
Causes of secondary polycythaemia
Chronic hypoxia (incl COPD) Renal cancer renal cyst hydronephrosis Hepatocellular carcinoma Cerebellar haemangioma
What is Fanconi anaemia
Inherited aplastic anaemia
Causes of haemolytic anaemia
Membrane defects Sepsis Sickle cell Thalassaemia Autoimmune Transfusion reaction Haemolytic disease of the newborn HUS DIC Malignant hypertension Mechanical valves Penicillin Malaria
What may precipitate sickling in sickle cell anaemia
Infection
DeHydration
Acidosis
Hypoxia
What type of thalassaemia is most common?
Beta thalassaemia
What is wergener’s granulomatosis
Necrotising small vessel vasculitis
Multi system disorder
Commonly involves lungs and kidneys
Associated with cANCA
What is polycythaemia rubra vera
High Hb due to myelo-proliferation
Potential to transform into acute myeloid leukaemia
What does the prothrombin time best represent?
The intrinsic pathway
The effect of heparins
Causes of iron deficiency anaemia
Menorhagia
Blood loss. E.g. GI
Hookworm
Malabsorption (coeliac)
Signs of iron deficiency anaemia
Koilonychia
Atrophic glossitis
Angular cheilosis
Post-cricoid webs
Where is folate absorbed
Duodenum and proximal jejunum
Causes of folate deficiency
Poor diet Pregnancy Coeliac Alcohol Phenytoin Sodium valproate Methotrexate Trimethoprim
Causes of b12 deficiency
Decreased dietary intake (vegan)
Decreased absorption - pernicious anaemia, gastrectomy, crohn’s, tropical sprue, ileal resection
Where is b12 absorbed
Terminal ileum (Bound to intrinsic factor)
Features of b12 deficiency
Pallor Mild jaundice Glossitis Red beefy tongue Subacute combined degeneration of the cord Paraesthesia Peripheral neuropathy Depression Psychosis Dementia
Management of a low-grade fever (No other symptoms) when giving a blood transfusion
Slow transfusion and prescribe paracetamol
Close monitoring
Presentation of an acute Haemolytic transfusion reaction
Starts within minutes Fever Chest pain Abdominal pain loin pain DIC Acute renal failure
Management of an acute Haemolytic transfusion reaction
Immediately stop transfusion Return blood and giving set Blood Bank Take blood for FBC, clotting screen and Coombs test ABC Fluid resuscitation Cryoprecipitate or FFP for DIC Transfer to HDU/ITU
Complications of massive blood transfusion
Hypothermia thrombocytopenia hyperkalaemia Hypocalcaemia Deranged clotting
What is DIC?
Acquired consumptive coagulopathy
Widespread inappropriate activation of the clotting cascade.
Conversion of fibrinogen To fibrin
Multiple thrombi –> End organ ischaemia
Intravascular haemolysis
Platelet destruction
Rapid consumption of clotting factors platelets and fibrinogen
Clotting studies in DIC
Prolonged PT
Prolonged APTT
Treatment of DIC
Correct cause
Platelets, FFP, cryoprecipitate
What is haemophilia A
X-linked recessive disorder of congelation
Cannot synthesise factor VIII due to gene mutation
Prolonged APTT (Extrinsic clotting Cascade)
Normal PT (Intrinsic clotting Cascade)
What is haemophilia B
Christmas disease
Inability to synthesise factor IX
Prolonged to APTT
Normal PT
Presentation of congenital haemophilia
Presents when child begins to crawl or walk
Recurrent painful bleeds into joint and soft tissue
Arthropathy and neuropathy
Treatment of haemophilia A
Factor VIII concentrate -Regular infusion or when actively bleeding
Mild disease can be treated with desmopressin to release factor VIII from internal stores.
Treatment of haemophilia B
Factor IX concentrate
What causes a global reduction in clotting factor synthesis?
Chronic liver cirrhosis and hepatitis
Why is vitamin K essential in clotting factors synthesis
Carboxylation of clotting factors II, VII, IX, X
What does vitamin K deficiency do
Causes a hypocoagulable state
Common causes of inappropriately high INR While on warfarin
Dosing error,
Accidental overdose,
Drug interaction - Antibiotics, thyroxine, alcohol, antidepressants, aspirin, amiodarone, quinine
What is pernicious anaemia
Autoimmune loss of parietal cells
And / or intrinsic factor
Prevents absorption of b12
What does the schilling test do
Distinguishes pernicious anaemia from intestinal causes of b12 deficiency
What causes a macrocytic, megaloblastic anaemia with hypersegmented neutrophils
B12 deficiency
Management of b12 deficiency
IM hydroxocobalamin (preparation of b12)
1mg every other day until blood film normal
Then 1mg every 3m
Management of anaemia secondary to chronic renal failure
Exogenous erythropoietin administration
Which haemoglobin chain is not produced in a beta-thalassaemia
The beta-globin chain
Presentation of beta-thalassaemia major
Presents in 1st year of life Failure to thrive Lethargy Pallor Jaundice Hepatosplenomegaly Frontal bossing Long bone deformity
Treatment of beta-thalassaemia major
Regular blood transfusions
Regular iron chelation therapy - desferrioxamine
Or allergenic bone marrow transplant
Presentation of beta-thalassaemia minor
Mild anaemia
Usually asymptomatic
What are the four variants of alpha-thalassaemia
Asymptomatic - 1 gene corruption
Mild hypochromic anaemia - 2 gene corruptions
HbH disease - 3 gene corruptions
Death in uterine - all 4 genes corrupted
What drugs may trigger an autoimmune haemolytic anaemia
Methyldopa
Penicillin
Cephalosporins
Quinine
What is the direct Coombs test
Used to test for autoimmune hemolytic anaemia.
It detects RBC that are coated with autoantibodies
Coombs agent = antibodies which are added to the RBC and adhere to any antibodies on the RBC causing RBC agglutination
What is the indirect Coombs test
indirect Coombs’ test is done on the plasma.
It detects antibodies that are present in the bloodstream and could bind to certain red blood cells and destroy them.
Used in prenatal testing of pregnant women and testing blood prior to transfusion.
What is multiple myeloma
Multisystem disease
malignant proliferation of plasma cells
Investigation findings in multiple myeloma
Monoclonal band on serum Electrophoresis
Free immunoglobulin light chains in urine
Presentation of multiple myeloma
Lethargy Bone pain Pathological fracture Renal failure Amyloidosis Pancytopenia -due to marrow infiltration
Diagnosis of multiple myeloma
Two or more of:
- Marrow plasmacytosis
- serum/urinary immunoglobulin light chains (Bence-Jones protein)
- skeletal lesions (osteolytic lesion, pepperpot skull pathological fracture)
Management of multiple myeloma
Bone pain control with analgesia, bisphosphonate, orthopaedic intervention
Renal failure managed by increased fluid intake
Broad-spectrum antibiotics for infection
Erythropoietin for anaemia
Blood transfusion for pancytopenia
Prognosis of multiple myeloma
Death Within 4 years
Stem cell transplant offers hope of cure - but 30% mortality from treatment
Typical age of presentation of Hodgkin’s lymphoma
Bimodal age distribution
Peak onset in third and sixth decades
Presentation of Hodgkin’s lymphoma
Asymmetrical painless lymphadenopathy
Usually as single rubbery lymph-node - cervical or inguinal or axillary
Node may be painful after alcohol
B symptoms of Hodgkin’s lymphoma
Weight loss
sweating
pruritis
general lethargy
Diagnosis of Hodgkin’s lymphoma
Lymph node biopsy showing Reed-Sternberg cells
CT for spread and staging (Ann Arbor staging system)
Management of Hodgkin’s lymphoma
Early stage radiotherapy alone
Advanced/bulky disease radiotherapy and chemotherapy
What infection is Hodgkin’s lymphoma associated with
History of glandular fever
What virus is non-Hodgkin’s lymphoma associated with
Epstein Barr virus
HIV
Helicobacter pylori
Presentation of non-Hodgkin’s lymphoma
Painless lymphadenopathy
+/- Systemic symptoms
Diagnosis of non-Hodgkin’s lymphoma
Lymph node biopsy
Management of non-Hodgkin’s lymphoma
CHOP chemotherapy
What is Burkitt’s lymphoma
Type of non-Hodgkin’s lymphoma which frequently involves the jaw
Most often seen an African children with EBV
What is mycosis fyngoides
A cutaneous T-cell lymphoma
What is polycythaemia rubra Vera
Myeloproliferative disorder
Mutation of a single pluripotent stem cell
Causes excessive erythrocyte production
Features of polycythaemia rubra vera
Raised haemoglobin
raised red-cell account
raised Packed cell volume (Haematocrit)
Viscous blood –> Increased risk of thrombosis and paradoxical bleeding
Symptoms of polycythaemia rubra Vera
Headache
Lethargy
Pruritus
Pruritus is worse after bathing in warm water
Treatment of polycythaemia Rubra Vera
Venesection
Chemotherapy with hydroxyurea
Prognosis of polycythaemia rubra Vera
30% develop myelofibrosis
5% develop acute myeloid leukaemia
What is myelofibrosis
A myeloproliferative disorder characterised by replacement of erythropoietic bone marrow with inert fibrotic material.
Presentation of myelofibrosis
Bone marrow failure - Pancytopenia
Extramedullary erythropoiesis in the liver and spleen produces massive hepatosplenomegaly
Diagnosis of myelofibrosis
Pancytopenia blood film - tear drop poikilocytes
Dry bone marrow aspirate
Trephine biopsy showed densify fibrosis of bone marrow
Management of myelofibrosis
Blood transfusion
Chemotherapy
Splenectomy
A bone marrow biopsy with excess plasma cells occurs in what condition
Multiple myeloma
Most common leukaemia in children
Acute lymphoblastic leukaemia (ALL)
primarily affects 2-8 yo.
equal risk between males and females
Are leukaemias more common in males or females
ALL is equally common in both genders
all other leukaemias occur more frequently in males
Presentation of acute leukaemias
bone marrow failure:
Anaemia – tired, SOB on exercise, weakness
Bleeding and bruising – due to thrombocytopaenia
Infection – result of leukopaenia
Bone pain – result of bone marrow infiltration
auer rods are pathognomonic For what condition
AML
Is the presence of lymphoblasts in the blood more common in ALL or AML
ALL
Always present
(May or may not be present in AML)
Is the presence of bone and joint pain and hepatosplenomegaly more common in ALL or AML
ALL
Prognosis of ALL in childhood
Complete remission obtained in almost all patients.
80% alive without recurrence at 5 years.
Failure of treatment occurs most commonly occurs in those with:
a high blast count
a T(9:22) translocation
What age group does chronic myeloid leukaemia commonly affect
Almost exclusively an adult disease
peak age of incidence is 40-60 years.
What disease is characterised by the presence of the Philadelphia chromosome
CML
What cells does CML affect
CML affects the myeloid cells
i.e. basophils, neutrophils and eosinophils.
What is the natural progression of CML
The natural progression of CML is as follows: chronic phase → aggressive/accelerated phase → blast phase/crisis.
What is the most common leukaemia in adults
Chronic lymphocytic leukaemia (CLL)
mainly in later life
Median survival is 10 years
What cell abnormality is responsible for CLL
CLL results from a progressive accumulation of functionally incompetent B lymphocytes.
Presentation of CML and CLL
Many Asymptomatic,
or SOB due to anaemia, marrow failure immunosuppression, splenic pain, weight loss, fever and sweats, lymphadenopathy hepatosplenomegaly.
CML usually presents in the chronic phase
CLL is often asymptomatic and discovered incidently.
Management of CML
Imatinib ( tyrosine kinase inhibitor)
prevents the action of the BCR-ABL fusion protein = the abnormal protein produced by the Ph mutation
Continue indefinitely
Management of CLL
Chlorambucil first-line therapy
combined with prednisone
What is a Myelodysplastic syndromes (MDS)
generally considered to benprecursors to leukaemia.
30% with MDS will develop acute myoblastic leukaemia (AML).
generally occur in the elderly.
Usually associated pancytopaenia.
What is Acute promyelocyte leukaemia (APML)
an uncommon variant of AML
involves a specific translocation mutation, t(15:17).
almost always coagulopathy - this is often the cause of death.
What is a blast crisis
The acute terminal phase of CML.
Mortality is very high.
blast crisis = > 20-30% blast cells in the blood or bone marrow.
Symptoms include:
- rapid increase in proportion of blast cells
- fever
- bone pain
- fatigue
- increased severity of anaemia, e.g. fatigue
- increased severity of thrombocytopaenia, e.g. bleeding and/or bruising
- splenomegaly
- large clusters of blasts on bone marrow film
What is Richter syndrome
where CLL is transformed into an aggressive, large B-cell lymphoma.
Epstein-Barr virus may play a role in transformation.
Lymph node biopsy is necessary for diagnosis
H pylori increases the incidence of what lymphoma
gastric MALT lymphoma
What is MALT lymphoma
Mucos associated lymphoid tissue.
Most commonly occurs in the stomach.
Abnormallly large collection of lymphocytes and macrophages
Differentials of cervical lymph node enlargement
Infection - Acute
- Infective mononucleosis
- Toxoplasmosis
- Infected eczema
- Cat scratch fever – bartonella. .
- Acute childhood exanthema –Includes Measles, rubella and scarlet fever
Infection -Chronic
- TB. - HIV. - Syphilis. - Sarcoidosis
Malignancies - Primary
- Hodgkin’s / Non-Hodgkin’s lymphoma
- Chronic lymphocytic leukaemia / Acute lymphoblastic leukaemia
Malignancies - Secondary
- Naropharyngeal / Pharyngeal. - Thyroid
- Lung. - Breast. - Stomach
Others
- Rheumatoid arthirits
- Reaction to phenytoin
- Kawasaki’s syndrome
Post splenectomy prophylaxis rules
Cary a splenectomy card
Vaccination against pneumonia, HIB, Neisseria meningitides
Prophylactic amoxicillin (erythromycin) until age 15
What is the upper age limit for bone marrow transplant
55
Complications of bone marrow transplant
Graft vs host disease
Pneumonitis
Infection
Secondary malignancy
In CML do patients with or without the Philadelphia chromosome have a worse prognosis
Without Philadelphia = worse prognosis
What is tumour lysis syndrome
Seen I. Patients with a lymphoproloferative malignancy following chemotherapy.
Massive cell death releases k+, phosphate, uric acid.
Phosphate binds Ca2+
Hyperkalaemia, hyperphosphataemia, hyperuricaemia
Hypocalcaemia
Management of tumour lysis syndrome
IV fluids
Allopurinol (lower uric acid level)
Renal support
Correct electrolyte imbalance
What is the most effective way of preventing neutropenic sepsis in post-chemotherapy patients
Hand hygiene
Reverse barrier nursing
When do tear drop shaped cells appear on blood film
Myelofibrosis
Cause of idopathic thrombocytopenic purpura
Autoantibodies form against platelets
Usually seen after a viral illness e.g. Chicken pox
Causes of pancytopenia
Marrow infiltration in multiple myeloma
Severe megaloblastic anaemia
Aplastic anaemia
Hypersplenism
What is essential thrombocytopenia
Myeloproliferative disorder
Excess production of defective platelets derived from abnormal megakaryocytes in the bone marrow
Symptoms of essential thrombocytopenia
Headache
Digital ischaemia
Abdominal pain secondary to splenic infarction
Causes of warm autoimmune haemolytic anaemia
IgG
Idiopathic Leukaemia - CLL Lymphomas - non-Hodgkin's lymphoma Other autoimmune diseases - SLE Drug HIV infection
Causes of cold autoimmune haemolytic anaemia
IgM
Idiopathic Epstein-Barr virus and infectious mononucleosis Mycoplasma pneumoniae, non-Hodgkin's lymphoma CLL Mycoplasma pneumoniae
