Clinical Haematology Flashcards
What happens in CLL
Monoclonal proliferation of well differentiated lymphocytes (B cells in 99%)
Features of CLL
Anorexia, weight loss
Infections, bleeding
Lymphadenopathy (more marked than CML)
Complications of CLL
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia (10-15% of patients)
transformation to high-grade lymphoma (Richter’s transformation)
What is Meig’s syndrome
Ovarian fibroma with pleural effusion and ascites
Von Willibrand disease inheritance
Autosomal dominant in 80%
Most common inherited bleeding disorder
Tumour antigens - association with cancers PSA alpha-feto protein CEA (carcinoembryonic antigen) S-100 Bombesin
Prostate cancer Hepatocellular carcinoma, teratoma Colorectal carcinoma Melanoma, schwannoma Small cell lung carcinoma, gastric cancer, neuroblastoma
Features of Von Willibrand disease
Epistaxis and menorrhagia - behaves like a platelet disorder
haemoarthroses and muscle haematomas are rare
Most common inherited bleeding disorder
Role of Von Willebrand factor
Promotes platelet aggregation to damaged epithelium
Carrier molecule for factor VIII
Ix for Von Willebrand disease and results
APTT - prolonged
Moderately reduced factor VIII levels
Defective platelet aggregation with ristocetin
Drugs cleared by haemodialysis
BLAST barbiturates Lithium Alcohol (inc methanol) Salicylates Theophyllines
Management of Von Willebrand disease
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
When do you monitor LFTs for statins and at what level do you stop them?
Baseline, 3months and 1 yr
Stop treatment if ALT rises and persists >3x upper limit of normal
Who should receive a statin?
Pts with established CV disease (IHD, stroke, PVD, TIA)
10 yr CV risk >20%
T2DM pts with other CV RISK
What is the Philadelphia chromosome
what is it’s result
translocation 9-22
in >95% of patients with chronic myeloid leukaemia (CML)
codes for a protein with increased tyrosine kinase activity
presentation of chronic myeloid leukaemia
aged 40-50
anaemia, weight loss, abdominal pain
splenomegaly may be marked
Mx of chronic myeloid leukaemia
imatinib 1st choice (tyrosine kinase inhibitor associated with BCR-ABL gene defect)
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
tear drop poikilocytes on a blood film
myelofibrosis
causes of target cells (codocytes) on a blood film?
sickle cell (leads to autosplenectomy)
Hyposplenism (unable to remove damaged cells)
thalassaemia
iron def anaemia (decreasing haem content)
liver disease (defunct enzyme increasing cell surface membrane)
most common presenting features of myelofibrosis?
blood film findings?
lethargy
tear drop poikilocytes
Chronic lymphocytic leukaemia (CLL) Ix of choice
Blood film - smudge cells
Immunophenotyping - B cells (CD19 positive)
CD5 and CD23 normally positive in CLL
what is a Howell-Jolly body on a blood film?
what are the causes?
RBCs with remaining fragments of DNA, usually removed by spleen.
hyposplenism, asplenia, autosplenism from Sickle cell
what is the enzyme affected in Acute Intermittent Porphyria (AIP)?
Sx AIP
auto dom defective porphobilinogen deAminase
abdominal pain, neuropsychiatric Sx, hypertension and tachycardia
urine turns purple on prolonged exposure to sunlight
which enzyme is affected in porphyria cutanea tarda (PCT)
uroporphyrinogen deCarboxylase
photosensitive rash with bullae
features of Wiskott-Aldrich syndrome
inheritance
primary immunodeficiency B and T cells recurrent bacterial infections eczema thrombocytopenia x linked recessive - WASP gene
pathology of polycythemia rubra vera
what is the mutation?
myeloproliferative disorder of bone marrow stem cells –> increased RBC, neutrophils and platelets
JAK2 mutation is seen in 95% of pts
5-15% progress to myelofibrosis and AML
classical symptoms of thrombotic thrombocytopenic purpura
pentad: fever renal failure thrombocytopenia neurological symptoms (due to emboli) microangiopathic haemolytic anaemia (anaemia, jaundice, schistocytes on blood film)
pathology of thrombotic thrombocytopenic purpura
idiopathic or secondary (ca, preg, meds, HIV) inhibition of ADAMTS13 enzyme which breaks down vWF multimers –> increased platelet aggregation and thrombi
What are the biochemical derrangements in Antiphospholipid syndrome?
paradoxical rise in APTT
low platelets
inheritance of haemophilias?
x-linked recessive
What is the pathology of haemophilia A
deficiency in factor VIII (8) –> increased bleeding (prolonged APTT, normal PT)
what is the pathology of haemophilia B
deficiency in factor IX (9) –> increased bleeding (prolonged APTT, normal PT)
causes of warm autoimmune haemolytic anaemia
features of WAIHA
Mx
drugs: methyldopa
neoplasm: lymphoma, CLL
autoimmune dz: SLE
extravascular reaction (eg spleen), IgG mediated steroids, immunosuppression, splenectomy
causes of cold autoimmune haemolytic anaemia
neoplasia: CLL, NHL, Walenstrom’s macroglobulinaemia
infections: mycoplasma, EBV, CMV, varicella.
intravascular, features similar to Raynaud’s
responds less well to steroids.
Treatment of polycythemia ruba Vera
venesection 1st line
Hydroxycarbamide to decrease platelet count
(JAK2 positive in 95%)
What is the pathology behind factor V Leiden mutation?
Increased factor V resistance to activated protein C -> hyper-coagulable state (DVT/PE)
Mx of thrombotic thrombocytopenic purpura
Plasma exchange (1st choice) Steroids, immunosuppressants, vincristine
Prognosis marker for myeloma
B2-microglobulin - increased levels = poor prognosis
types of Hodgkin’s lymphoma:
best prognosis
worst prognosis
most common
best prog: lymphocyte predominant (5%)
worst prog: lymphocyte depleted (rare)
most common: nodular sclerosing (70%) - associated with lacunar cells
Poor prognostic factors in CLL
male >70 fast lymphocyte doubling time raised LDH CD58 expression positive
factors associated with a poor prognosis in Hodgkin’s lymphoma
male
>45 years
stage 4 disease
Hb <15
name and define the 4 types of crisis seen in sickle cell
thrombosis crisis - painful, precipitated by infection/deoxygenation/dehydration
sequestration - sickling in organs -> pooling of blood
aplastic - secondary to parvovirus infection. Sudden fall in Hb
Haemolytic - rare. Hb drop due to haemolysis
features of Paroxysmal Nocturnal haematuria
pathology
haemolytic anaemia any/all blood lines may be affected haemoglobinuria - classically dark morning urine Thrombosis eg Budd-Chiari Aplastic anaemia may develop low CD55 and 59
Mx of paroxysmal nocturnal haematuria
replacement blood products
anticoagulant (increased risk of VTE)
?stem cell transplantation
pathology of Hereditary Spherocytosis
inheritance?
most common hereditary haemolytic anaemia in causcasians
Auto Dom defect in RBC cytoskeleton ->RBC destruction by spleen
features of spherocytosis
Dx
Mx
FTT, jaundice, gallstones, splenomegaly,
aplastic crisis secondary to parvovirus infection
Dx with osmotic fragility test
Mx: folate replacement, splenectomy
what is Burkitt’s lymphoma
associated gene translocation and disease
high grade B cell lymphoma
t(8:14)
EBV
features of tumour lysis syndrome
Mx
increased K, Phos, Urate low calcium, ARF Rasburicase (urate oxidase recombinant) given prior to chemo. converts uric acid to allantoin, better renally excreted. High risk in Burkitt's lymphoma
features of Waldenstrom’s macroglobulinaemia
IgM paraproteinaemia weight loss hyperviscosity syndrome hepatosplenomegaly lymphadenopathy cryoglobulinaemia
thymoma associations
MG (30-40% of patients with thymoma) red cell aplasia dermatomyositis SLE SIADH
Multiple myeloma symptoms
rapidly increasing back pain which doesn’t vary with time of day or movement.
raised ESR, normal CRP
renal failure
normocytic anaemia
pathology of multiple myeloma
accumulation of malignant plasma cells, generally derived from 1 clone in the bone marrow.
production of a monoclonal immunoglobulin
Dx of multiple myeloma
Rx
Bence Jones protein in urine.
>10% plasma cells in bone marrow aspirate
Rx: melphalan chemotherapy. Autologous transplant if <65
features of AML
hyperviscosity symptoms (headache, fits, confusion, focal neurology, coma)
gum hypertrophy (deposits of leukaemic cells)
Auer rods present in bone marrow
positive stain for Sudan Black and myeloperoxidase
Ix of ALL
positive Periodic acid-Schiff stain and non-specific esterase
Rx of cold auto-immune haemolytic anaemia
keep warm
folic acid supplements (for all haemolytic anaemias)
avoid FFP (well thawed!)
chlorambucil and rituximab (anti CD20) - removes B cells producing the IgG
Coag changes seen in anti phospholipid syndrome
Prolonged APTT with normal PT
Due to lupus antibody
Causes pro thrombotic state
Lab test features of a factor 7 deficiency
Only factor that is unique to PT so will have prolonged PT with normal APTT.
Autosomal recessive, rare
Features of iron overload
Mx
Causes
Grey skin, heart failure, diabetes
Iron chelation - deferoxamine
Secondary to chronic blood transfusions
Features of multiple myeloma
CRAB calcium (raised) renal failure anaemia (normocytic normochromic) bone pain (and lytic lesions)
features of monoclonal gammopathy of unknown significance (MGUS)
low paraprotein band IgG <2
asymptomatic and normal blood count
1% progress to myeloma (therefore MGUS is premalignant)
Indications for platelet transfusion
platelets <10
pts with marrow suppression - chem/radiotherapy, marrow infiltration
contraindications for platelet transfusion
thrombotic thrombocytopenic purpura
microangiopathic anaemia, thrombocytopenia, fever, neuro symptoms, RF
