Haematology Flashcards
Causes of secondary thromocytosis?
Bleeding, infection, trauma, thrombosis, infarction, Fe deficiency, hyposplenism
Acquired thrombophilias?
Antiphospholipid antibodies
Polycythaemia
Thrombocythaemia
Antophospholipid syndrome What antibodies? Presentation? Coagulation results? Diagnosis?
Abs = lupus anticoagulant, anticardiolipin Abs, anti-beta 2 glycoprotein 1 Abs
Presentation = recurrent thromboembolism/miscarriage
Coagulation = prolonged. More sensitive test is DRVVT (dilute Russell viper venom time)
Diagnosis =
- Presence of Abs on repeat test 12 weeks apart
- Failure of coagulation tests to correct on addition of normal plasma
- Coagulation tests correct on addition of excess phospholipids
Indications for exchange transfusion in sickle cell disease?
Frequent severe pain crisis
CNS sickling
Chest syndrome unresponsive to conservative Mx
Priapism
Peri-operatively/pregnancy i history of bad sickling
Cause of polychromasia?
Young RBC
Cause of teardrop RBCs?
Myelofibrosis
Chronic lymphocytic leukaemia
Features of poor prognosis?
Indications for management?
Management?
Prognosis
- male, >70
- lymphocyte >50, polymorphs >10%, doubling time <12 months
- raised LDH
- CD38 +ve, TP53 mutation
- 17p deletion
Indications
- Progressive marrow failure
- Massive >10cm/progressive lymphadenopathy
- Massive >6cm/progressive splenomegaly
- Progressive lymphocytosis: >50% in 2 months or doubling in 6
- Systemic symptoms: weight loss >10% in 6 months, fever >38 for 2 weeks, extreme fatigue, night sweats
- Autoimmune cytopaenias
Management
- Often none required
- PRIOR TO CHEMO: p53 tumour suppressor gene analysis. Deletion/mutation = worse prognosis + resistance to standard chemo
- Chemo of choice = FCR (Fludarabine, cyclophosphamide, rituximab)
- Fludarabine is associated with profound lymphopenia. Prophylactic Co-trimoxazole essential to avoid pneumocystitisi no
Cause of spherocytosis?
Any haemolytic anaemia
Hereditary spherocytosis
Cause of sideroblastic anaemia?
Failure to incorporate Fe in Hb molecule –> Fe accumulation in mitochindria
Congenital
Acquired primary - myelodysplastic disorder
Acquired secondary - Alcohol, malignancy, drugs (e,g, anti-TB), connective tissue disorder, heavy metal poisoning
Multiple Myeloma Definition? Clinical presentation? Pathologic features? Imaging?
Clonal proliferation of plasma cells producing a monoclonal Ig. Clonality = all diseased cells originating from one parent cell
Presentation
- CRAB: Ca elevated, Renal dysfunction, Anaemia, Bone disease
- Also common: weight loss, fatigue
- Less common: parasthesia, hepato/splenomegaly, fever
Pathologic features
- Monoclonal protein in majority on serum electrophoresis. IgG most common then IgA then kappa/lambda light chain only then IgD/A/M. hypogammaglobulinaemia of unaffected Ig may be seen (all of them in non-secretory myeloma).
- BM biopsy. Clonal plasma cell >10% if major criteria for diagnosis
- Urinealysis: myeloma cast nephropathy –> negative dip. Renal involvement e.g. AL amyloidosis/light chain deposition –> positive dip. bence Jones protein seen in light chain only myeloma
- Peripheral smear: rouleaux formation most common. May see leukopenia/thrombocytopenia
Imaging = whole body MRI to investigate for bone disease
Causes of folate deficiency?
Poor intake
Malabsorption (IBD/surgical resection)
Inc. requirement - pregnancy, haemolysis
Cause of sickle cell disease?
valine substituted for glutamic acid in position 6 of beta globin chain on chromosome 11
Clinical syndromes in sickle cell disease
Cause?
Possible precipitants?
Examples?
Cause = occlusion of small blood vessels by sickled cells Precipitants = hypoxia, dehydration, infection. Often none identified Examples = Pain crisis, chest syndrome, vaso-occlusive stroke, priapism, dactylitis, splenic sequestration crisis, aplastic crisis
Acute Promyelocytic leukaemia Associated chromosomal abnormality? Histology? Unique clinical feature? Treatment?
Chromosome abnormality = t(15;17)
Fusion of PML and RAR-alpha (retinoic acid receptor)
Histology - Auer rods, faggot cells
Clinical feature = DIC/thrombocytopenia often at presentation
Treatment
- DIC –> tranexamic acid, FFP, platelets
- All-trans retinoic acid
Management of sideroblastic anaemia?
Remove cause if able
High dose pyridoxine + folate
?Erythropoeitin
RBC Tx - can worsen Fe overload
What is Felty’s syndrome?
Rheumatoid arthritis + splenomegaly + neutropenia
Multiple myeloma vs MGUS?
MM Vs MGUS
- High paraprotein vs low paraprotein (<30 g/L for IgG)
- Rising paraprotein vs stable paraprotein
- Other Ig levels low vs other Ig levels normal
- CRAB vs no CRAB
Use of hydroxycarbamide in sickle cell disease?
Side effects?
Used to increase HbF levels
SEs: BM suppression, subfertility, teratogenicity
Cause of fragmented RBCs?
MAHA
Causes of macrocytosis with normoblastic BM?
High reticulocyte count Liver disease (impaired lipid manufacturing for RBC membrane) Alcohol (BM toxicity, liver disease) Myxoedema Pregnancy
Aplastic anaemia
Blood results?
Causes?
Bloods = pancytopenia. Reduced reticulocyte count
Idiopathic (autoimmune)
Drugs - anti-thyroid, anti-seizure, gold etc.
Post-hepatitis (virus affects hepatocytes + BM stem cells)
Chemotherapy/radiation (e.g. azathioprine/mercaptopurine in Pts with low thiopurine methyltransferase levels)
Indications for splenectomy?
Changes seen after splenectomy?
Traumatic rupture
Autoimmune destruction of blood cells
Haematological malignancy (associated with massive splenomegaly/pain/other complications)
Congenital haemolytic anaemias
Changes
- Howell-Jolly bodies (nuclear remnants in RBCs)
- Target cells, thrombocytosis, increased aniso + poikilocytosis
- Decreased IgM. Polyclonal T lymphocytosis. Enhanced neutrophilia in infection
Chronic lymphocytic leukaemia
Clinical features?
Blood results?
Investigation of choice?
Features
- Commonly asymptomatic detected on routine bloods
- B symptoms
- Painless lymphadenopathy. Splenomegaly (less common than CML), hepatomegaly, skin manifestations
- Acquired immunodeficiency, immune complications (e.g. haemolysis, thrombocytopenia)
- Lymphocytosis –> high viscosity
Bloods
- Lymphocytosis
- ?cytopenias. Usually mild
- ?hypo/hyper gammaglobulinaemia
Investigation = Immunophenotyping
- 95% of cases are B cell lineage
- B cell: CD19, CD23
- T cell: CD5
Thrombotic Thrombocytopaenic Purpura
Pathology & causes?
Clinical & biochemical features?
Main management?
Path = ADAMST13 deficiency --> failure to cleave high molecular weight vWF --> formation of platelet microthrombi Causes = post infection, pregnancy, tumours, SLE, HIV, drugs (e.g. ciclosporin, OCP, penicillin)
Clinical = often fever, cerebral & cardiac dysfunction. Renal dysfunction less marked than in HUS Biochemical = typical MAHA, thrombocytopaenia, normal coagulation. Reduced ADAMST13
Management = FFP infusion + plasma exchange
Diagnostic criteria for multiple myeloma?
Diagnosis - Clonal BM plasma cells >10% AND EITHER of the following - Related organ or tissue damage (CRAB) - Biomarker of near inevitable progression to end organ damage (SliM - Sixty% clonal plasma cell in BM, Light chain ratio >100, MRI with 1 or more focal lesions)
Disseminated Intravascular Coagulation
Laboratory features?
Causes?
Lab features
- All coagulation prolonged
- Low fibrinogen, high fibrin degradation products
- Cosumption thrombocytopenia
Causes
- Obstetric: retroplacental haemorrhage, retained fetus, amniotic embolism, severe pre-eclampsia
- other: crush, sepsis (esp. tosin producing staph aureus, clostridia), Haemolytic blood Tx reaction, Malignancy (esp associated with tumour cell necrosis)
Alpha thalassaemia genotypes?
Normal = (aa)(aa)
a+ Heterozygous (a-)(aa) = mild microcytosis, no anaemia
a+ heterozygous (a-)(a-) OR ao homozygous (aa)(–) = slightly anaemia. Low MCV
HbH disease (a-)(–)= microcytic + hypochromic anaemia with splenomegaly. tetramer of b Hb form HbH
Major (–)(–) = death in utero
Hodgkin's Lymphoma Common clinical features? Histology and subtypes? Blood findings? Staging? Management?
Clinical
- Lymphadenopathy (non-tender, rubbery)
- Mediastinal mass –> cough, SOB, chest pain. Effusions are uncommon. SVC syndrome rare.
- B symptoms
- Pruritis
- Alcohol induced pain less common
Histology:
- Reed-Sternberg cells (Giant cell often with mirror image nuclei)
Subtypes:
- Lymphocyte predominant = reactive T cell infiltration (best prognosis)
- Nodular sclerosis = fibrous bands separate nodules of Hodgkin’s tissue (most common 70%)
- Mixed picture
- Lymphocyte depleted = no infiltrating lymphocytes (worst prognosis)
Bloods
- Common: Neutrophilia, thrombocytosis, anaemia. May be eosinophilia
- Raised ESR
- Raised LDH (guide to volume of disease)
Haemloytic uraemic syndrome
Causes?
Triad of features?
Management?
Hereditary = complement gene mutations, coagulation pathway mutations, cobalamin C mutations
Acquired infectious = shiga producing E coli 0157 (90% of cases), strep pneumoniae, HIV
Acquired non-infectious = complement Abs, drugs, other conditions (e.g. SLE, pregnancy)
Features
- MAHA (anaemia, schistocytes)
- Thrombocytopenia
- Deranged kidney function
Management
- Supportive
- Severe disease ?ecilizumab (complement C5 Ab) ?plasma exchange
Causes of macrocytic anaemia with megalobblastic errythropoeisis?
B12 deficiency
Folate deficiency
Drugs affecting BM DNA synthesis (e.g. methotrexate, azathioprie, hydroxycarbamide)
Immune thrombocytopenia
Associated conditions?
Management?
Associated = SLE, autoimmune haemolytic anaemia, viral infections (HIV, hep C, EBV), antiphospholipid syndrome, helicobacter gastritis
Management
- Steroids
- IV Ig if life threatening bleeding and platelet Clint needs to rise quickly
- steroid resistant –> splenectomy, IV IG, anti-D in D+ve (coats RBCs which are then preferentially destroyed), rituximab
Causes of haemolysis?
Autoimmune (cold agglutinin, warm AIHA, PNH)
Congenital (haemoglobinopathies, RBC membrane defects e.g. spherocytosis, RBC enzyme defects e.g. G6PD deficiency)
DIC
Drug induced (immune, G6PD, thrombotic microangiopathy)
Transfusion (acute & delayed reaction)
Other (mechanical at heart valves, RBC parasite e.g. malaria, thrombotic microangiopathy, clostridial sepsis etc.)
Causes of microangiopathic haemolytic anaemia?
DIC Haemolytic uraemic syndrome Thrombotic thrombocytopeanic purpura Malignant HTN Severe pre-eclampsia
Anticoagulants LMWH mechanism + monitoring? Warfarin mechanism? Dabigatran mechanism? Rivaroxaban mechanism? Apixaban mechanism?
LMWH
- Anti-factor Xa. Weak antithrombin compared to heparin
- Monitor with anti-Xa levels with prolonged courses
Warfarin
- Inhibits hepatic synthesis of vitamin K dependent factors (2, 7, 9, 10, protein C). Initially prothrombotic = requires bridging anticoagulation on initiation.
Dabigatran
- Direct thrombin inhibition
Rivaroxaban & apixaban
- Direct Xa inhibition
