Haematology Flashcards
(47 cards)
1
Q
What are the late complications of BMT?
A
- treatment related: gonadal toxicity, neuropathy
- chronic GVHD
- infection
- relapse
- secondary malignancy
2
Q
What are signs of acute GVHD?
A
Skin: maculopapular rash
GI: diarrhea, N/V
Liver: deranged LFT/bili, hepatomegaly
3
Q
What is the treatment of acute GVHD?
A
- topical steroid
- systemic steroids: methylpred
- octreotide for diarrhea
Second line agents: MMF, etanercept
4
Q
What are the features of chronic GVHD?
A
> 100 days Skin: scleroderma-like GI: dry oral mucosa with ulceration a, dysphagia, chronic diarrhea, malabsorption Lung: bronchiolitis obliterans Blood: thrombocytopenia
5
Q
What is the treatment of chronic GVHD?
A
- enrol in clinical trial
Otherwise: - prednisone
- add CNI if no improvement after 4-6/52 of pred
6
Q
What is the genetic abnormality in CML?
A
Bcr-ABL - always on tyrosine kinase
7
Q
What is the treatment of CML?
A
Stem cell tx (may be curative)
TKI: imatinib
Chemotherapy for palliation
8
Q
What are the B symptoms?
A
Fever
Wt loss
Night sweats
9
Q
What are reed sternberg cells associated with?
A
Hodgkin lymphoma
10
Q
What is the management of Hodgkin Lymphoma?
A
- RTx
2. Chemo: ABVD, BEACOPP
11
Q
What is the management of NHL?
A
High grade: Rituximab-CHOP
BMTx
12
Q
What are the complications of lymphoma treatment?
A
- effects of radiation: fibrosis, pericarditis
- secondary malignancies: leukaemia, breast, skin
- fertility: reduced, teratogenic effects of chemo
13
Q
What causes microcytic anemia?
A
- iron deficiency
- thalassemia
- anemia of chronic disease
14
Q
What causes normocytic anemia?
A
- acute bleeding
- bone marrow failure: aplastic, mds, infiltrative disease
- CKD
- hemolysis
15
Q
What are the causes of macrocytic anemia?
A
- B12 or folate deficiency
- alcohol
- liver cirrhosis
- mds
16
Q
What investigations for anemia?
A
- FBC, Blood film
- reticulocytes: low if BM issue, high if loss/destruction of RBC
- iron studies
- b12/folate
- intrinsic factor ab
- hemolysis: low haptoglobin, raised bili, DAT
- BM biopsy
- TFT
- electrophoresis for hemoglobinopathies
17
Q
What are the clinical features of MM?
A
CRAB: - hypercalcemia - renal failure - anemia - bone pain Also, fractures, amyloidosis, cord compression
18
Q
What investigations for MM?
A
- FBC, ESR, CMP, EUC
- serum and urine EPG/IEPG: monoclonal protein
- serum free light chains
- B2 microglobulin for prognostication
- urine bence Jones
- bone marrow biopsy
- XR skeletal survey
- MRI if concern for spinal cord compression
- urate
19
Q
What is the treatment for MM?
A
Chemotherapy - high dose steroid plus thalidomide/lenalidomide - bortezomib - cyclophosphamide ATSCTx Symptom control: - RTx to bony lesions, bisphosphonates - allopurinol for raised urate from treatment
20
Q
What are the prognostic factors in MM?
A
- 13q deletion
- high b2 microglobulin
- poor ECOG
- anemia
- hypercalcemia
- renal failure
21
Q
What are the early complications of BMTx?
A
- Infection
- Graft Failure
- acute GVHD
22
Q
What are indicaitons for BMTx?
A
1) Brief if long time ago, only spend more time if a) recur b) relevant now
2) What?
3) How presented? (brief) = e.g. “Allogenic BMT done for AML for which he presented with
pancytopenia and Hb of 60”
4) Risk profile - cytogenetics if relevant
5) Mx prior to Tx (brief) - mention relevant chemos if going to have long term SEs e.g:
1) Anthracyclines: cardiac toxicity
2) Vinca alkaloids: neuropathy
6) Donor? Well matched?
7) Blood group
8) CMV status
9) Recipient conditioning - myeloablative chemo/ full body radiation
23
Q
What are early complications of BMTx?
A
1) Induction related: mucositis, cystitis, interstitial pneumonitis (usually CMV), renal impairment
2) Graft failure
3) Infection
4) Immunodeficiency
5) Acute GVHD (within 3/12) - rash (can be blistering), GI (similar to crohn’s), Liver function derangements
6) VOD (veno-occlusive disease - sinusoidal obstructive disease of the liver - typically within 1 month, presents with triad of raised Bili (jaundice), fluid retention (ascites) and tender hepatomegaly. Treatment: Defibritide
24
Q
What are late complications of BMTx?
A
1) Treatment related: Gonadal toxicity, Cataracts, Neurological
2) Chronic GVHD (> 100 days) - rare to persist >3 yrs
- Sicca syndrome (like Sjogren’s) = dry eyes, mouth (xerostomia), leading to ulceration, pain and poor dentition. Needs intensive topical tx (steroid drops)
- Skin: patchy skin disease. Most feared form resembles SSc (sclerodactyly, restricted movement, reduced chest expansion)
- Lung: obstructive pattern- Bronchiolitis obliterans, chronic cough, SOB, wheeze; Fatal if progressive
- GI: milder IBD symptoms
- Abnormal LFT - classically mixed pattern: ↑ALT, ↑GGT
3) Infection
4) Status/Relapse of original treated condition
- Remission? result of latest PET/ bx?
5) Second malignancy
25
Infections and prophylaxis post BMTx?
1) More common post BMT than solid organ
2) Prophylaxis with Valaciclovir, TMP-SMX and Fluconazole for 6 months
3) Post transplant, functionally hyposplenic - may give prophylaxis against encapsulated bacteria, ensure vaccinations up to date (childhood vax no longer applies)
26
Drug SEs post BMTx?
Post BMTx Drug SEs: Steroids, CNI, MMF
- Usually weaned off immunosuppression by 6 months
- Suggestive of GVHD if still on > 6 months
27
Very Late SEs (> 3 years) post BMTx?
1) Malignancy risk
2) Endocrine - thyroid, hypogonadism, infertility
3) Vision
4) Psychiatric - depression, effect on work, function
28
What is the management of Haemophilia A?
"A and B involve 8 and 9; FHx 70%; Sporadic 30%"
- Avoid Aspirin & NSAIDs (NSAIDS inhibit platelets, although COX-2 inhibitors celecoxib platelets are spared)
- DDAVP = tx of choice in mild-‐moderate haemophilia
- Recombinant FVIII/ FVIII concentrate (regular prophylaxis if severe disease c frequent bleeds)
- Dose of recombinant factor 8 = 15 - 30 units/ kg
- FFP/ CPP
- Dental care (Aim to avoid need for extractions)
- Restrictions re: contact sports
- Travel issues (FVIII supply, equipment etc)
29
What is the management of Haemophilia B?
"A and B involve 8 and 9; FHx 70%; Sporadic 30%"
- CHRISTMAS DISEASE FIX deficiency/ dysfunction
- X‐linked recessive; 1/100,000 males affected
- Clinically indistinguishable from Haemophilia A
- Management: FFP Recombinant FIX
- Haem B - longer half life of recombinant factor 9
- NB: Don’t use Prothrombinex to due thrombotic risk.
30
What causes recurrent bleeds in Haemophilia on prophylactic factors?
- Prophylactic factors to maintain basal level ~ 1% (makes spontaneous bleeds less likely)
- Typically dosed 3 times a week, half life of recombinant factor about 12 hrs
- If recurrent bleeds - think of inhibitors developing. Very difficult to treat. Usually develop within first 50 treatment days. Use bypass agents, but they are less effective
31
What are late complications of Haemophilia?
- Arthropathy - joint destruction, marked thickening and proliferation of synovium. MRI useful for diagnosing this. May require synovectomy
- Venous access may become an issue.
- New treatments coming through are subcut injections
32
=========================
Anaemia - categorised by cell size
What are the causes of Microcytic anaemia?
What are the causes of Macrocytic anaemia?
What are the causes of Normocytic anaemia?
>Microcytic - Mnemonic "Small Typically Iron"
-Sideroblastic
-Thalassaemia (usu high RBC count >5Bill/L)
-Iron deficiency
>Macrocytic - "My Blood Has Large Erythrocytes"
-Myelodysplasia (normoblastic, round macrocytes)
-B12/fol deficiency (megaloblastic, with oval macrocytes and hypersegmented neutrophils; failed DNA synth; likely if MCV >110fL)
-Haemolysis; Hypothyroidism (macro or normocytic)
-Liver disease
-Embryo (pregnancy)
>Normocytic (76-96fL) - "Exclude Chronic Anaemia"
-Endocrine (hypopit, hypothyroid, adrenal)
-Combined deficiency; Chronic disease (cancer, rheumatic disease)
-Acute blood loss/Aplastic
33
Anaemia
| What are the causes of congenital haemolytic anaemia?
>Mnemonic: "MEH" Membrane/Enzyme/Haemoglobin
-Membrane: Spherocytes (hered spher. most common, and is auto dominant), Elliptocytosis
-Enzyme: G6 PD (Glucose 6 Phos dehyd) deficiency - it maintains important antioxidant glutathione
-Haemoglobin: Thalassaemia, Sickle Cell Disease
>Presentation: +ve FHx, anaemia, splenomegaly, jaundice
>Risks/precipitants: infection, oxidation from drugs like dapsone, quinine and nitrofurantoin
>Ix: film for spherocyte, elliptocyte,
34
What are the natural anticoagulants?
>Mnemonic: "AP"TT
>Anti-thrombin III
-Can be deficient in nephrotic syndrome; get arterial and venous thrombosis
>Protein C + S
-Factor V Leiden mutation is auto-dominant, and prevents Protein C/Factor V from stopping the clotting cascade
-Protein C/S deficiencies are less common
35
What are the causes of excessive bleeding?
>Capillary/Platelet/Coagulation
>Capillary
-Inherited: collagen diseases (such as Ehlers Danlos); Hereditary haemorrhagic telangiectasia
-Acquired: severe infection, purpuras- senile, steroid, Henoch-Schonlein
>Platelet
-ITP: young females +/- splenomegaly
-Marrow infiltration (secondaries, leukaemia)
-Marrow aplasia (drugs, viral)
>Coagulation
-Anticoagulant treatment
-Haemophilia A or B (Haemoph.A is x-linked recessive of factor 8; Haemoph.B lack factor 9)
-Von Willebrand's disease (most common bleeding disorder in the west; auto dominant; adhesion of platelets to damaged vessel walls; bruising menorrhagia and epistaxis)
36
What are the causes of severe eosinophilia?
| Causes of severe eosinophilia with abnormal CXR?
>Severe Eos. (>5 bil/L)
-mnemonic "Painful Blisters"
-Parasitic infection (not common in the west)
-Blistering skin infections (Pemphigus, pemphigoid, eryth. multiforme)
>Severe Eos. + abnormal chest infection
-mnemonic "High Eosinophils + Lung Trouble"
-Hypereosinophilic syndrome (eos., HFPEF, hepatosplenomegaly)
-Eosinophilic pneumonia
-Leukaemia (eosinophilic)
-Tropical pulmonary eosinophilia
>Less Severe Eosinophilia (0.5-2 bil/L)
-asthma, rhinitis, drug allergies (sulfonamides, nitrofurantoin), Churg-Strauss, Hodgkin's lymphoma
37
What are the causes of high ESR >100?
| What is the differential for PMR?
>Mnemonic "Vasculitis May Prolong Sedimentation"
- Vasculitis
- Myeloma (disease of elderly; high immunoglobulins; risk of arterial and venous thrombosis)
- Polymyalgia Rheumatic (pain and stiffness in shoulder and pelvic girdle, rare <50yrs, associated GCA, muscle weakness is NOT a feature- if this is present suspect polymyositis; treatment is with high dose steroids)
- Sepsis
38
What are the common causes of immunodeficiency?
"Drugs May Cause Lowered Immunity"
- Drugs- phenytoin, penicillamine can induce hypogamma
- Myeloma- high levels of monoclonal gamma-globs have an immunoparetic effect, suppressing body's immune response to antigens (note the immunosuppressive effect of immunoglobulins is used to suppress autoimmune response in conditions like GBS)
- Common Variable Hypogammaglobulinaemia - this is primary; the rest secondary
- Lymphoma/Leukaemia (CLL)- associated with hypogamma
- Infection (HIV) impairs cell-mediated (CD4 T) immunity;
- (nephrotic syndrome also loses gammaglobulins)
39
Which form of leukaemia is most common in children?
Mnemonic "ALL the kids respond"
>Acute Lymphoblastic (ALL) most common in children
-more than 90% respond; and 70% cured
-acute associated with blasts, and rapid progression
-WCC may be raised/normal/low; the blasts are key
-AML vs ALL - AML have Auer rods- small inclusion bodies
-present with bone marrow failure: infection, anaemia, bleeding
>CML- suspect if high WCC (typical>50 neutrophils)
>CLL- suspect if high WCC (typical>15 lymphocytes)
40
What is the blood film and presentation of CLL?
Mnemonic CLL is the "B disease"
-B lymphocytes (95%)- initially just high WCC
-Bone marrow failure (anaemia, infection, bleeding)
-Bleeding
-Broken cells (smear cells)
>M: chlorambucil (1st line)
- treat folate deficiency (high turnover)
41
What is the onset, blood film and pathology of CML?
| DDx for splenomegaly and myeloid precursors?
CML "Myeloid Leukaemia Patient"
-Middle age
-Leukoerythroblastic picture (myeloid precursors, and nucleated RBCs)- ddx = marrow infiltrate or severe stressors or sepsis
-Philadelphia chromosome +ve (almost all; translocation of long arms t(9:22) chromosomes)
>DDx for splenomegaly and myeloid precursors?
-myelofibrosis: Philadelphia -ve (and high NAP neutrophil alk phos score)
42
Microangiopathic haemolytic anaemia
| What are the causes of MAHA?
"Ma H A Causes Blood Vessel Damage"
-Mucinous adenoca
-HUS/TTP and aHUS (haem uraemic synd; thrombotic thrombocytopaenic purpura; HUS is likely in E.Coli O157:H7; shiga toxin, gastro with fever and renal impairment; TTP due to ab to ADAMS which drops <10%; if ADAMTS13 levels >10% and AKI, then likely aHUS- check c3,c4,factor H, I; aHUS responds to eculizumab; factor H may respond to plasmapharesis and immunosuppresives)
-Accelerated HTN
-Connective tissue disease
-Burns
-Vasculitis
-DIC Disseminated Intravascular Coagulation
>Features: fragment (helmet) cells, schistocytes
43
What are the causes of pancytopaenia?
| Causes of pancytopaenia with raised MCV?
>Pancytopaenia: "My Spleen Injures Cells"
- Marrow infiltration
- Spleen (hypersplenism)
- Indiopathic acquired
- Congenital (Fanconi's anaemia - auto recessive, bone marrow failure, developmental abnormalities, reduced life expectancy)
>Pancytopaenia/High MCV:
- "Impaired Marrow Produces Some Big Cells"
- Infections EBV
- Myxoedema/Myelodysplasia
- PNH Parox nocturnal haemoglobinuria
- SLE
- B12
- Cytotoxics
44
What are the causes of polycythaemia?
>"Primary/Secondary/Inappropriate"
- Primary: Polycythaemia rubra vera (independent of EPO; typically raised platelets and neutrophils unlike the other causes)
- Secondary: Chronic lung disease, R-to-L cardiac shunts often congenital, High altitude (hypoxia=> elevated EPO)
- Inappropriate(Tumours): renal, liver brain (elevated EPO without hypoxic stimulation)
45
What are the causes of thrombocytosis?
>Mnemonic: "Massive Bleeding Increases Platelet Count Significantly"
- Myeloproliferative disease
- Bleeding (transient)
- Inflammation (transient) / Iron deficiency (reduced MCV)
- Primary thrombocytosis
- Connective Tissue disease/Cancer
- Splenectomy (see Howell-Jolly bodies)
46
What are conditions that cause both arterial and venous thrombosis?
>Mnemonic "Pretty Sticky Blood Thromboses All Vessels"
- PNH (membranes lysed by complement; dark urine and thrombosis; haemolytic anaemia)
- Sickle Cell
- Behcet's syndrome (orogenital ulceration; pathergy is papules >2mm at trauma e.g. injection sites)
- Thrombophilia
- Antiphospholipid syndrome (clots, miscarriage and livedo reticularis)
- Vasculitides
- (homocystinuria)
47
Which are the vitamin K dependent factors?
What is the half life of heparin?
How common is heparin induced thrombocytopaenia?
- vitamin K dependent factors: 2/7/9/10
- heparin half life - 2 hrs; APTT (not useful for LMWH which is predictable and does not raise APTT- is monitored with anti Xa if long term use)
- HIT occurs in 1-5%; subsequently one third of them may suffer from arterial and/or venous thrombosis (test AntiPF4 platelet factor 4)
