L32 - Practical approach to the investigation of haematological disorders Flashcards
Classify and list common causes of hyper- and hypoproliferative anaemia?
Hyperproliferative:
- Thalassaemias/haemoglobinopathies/membranopathy/ enzymopathy
- Haemolytic anaemia / haemolysis
Hypoproliferative:
- Nutrition deficiency
- Primary BM failure
- Drug/ toxin-induced
- Primary BM pathologies (infiltrative)
List all the subtypes of Immune- cause haemolytic anaemia?
1) Autoimmune: e.g. SLE, CLL, Mycoplasma infection, lymphomas…etc
Warm – primary vs. secondary
Cold – primary vs. secondary (lymphoma, autoimmune diseases)
Drug-induced (e.g. methyldopa)
2) Alloimmune (antibodies against transfused RBCs):
- Acute hemolytic transfusion reaction (e.g. ABO)
- Delayed HTR - anti-Jka /Jkb
List 6 causes of Microangiopathic Haemolytic anaemia?
- Disseminated intravascular coagulation (DIC)
- Thrombotic thrombocytopenic purpura (TTP)
- Prosthetic heart valves
- Malignant hypertension
- Systemic vasculitis
-Pregnancy-related complications
(Haemolytic-uraemic syndrome (HUS))
List some causes of Thrombotic thrombocytopenic purpura (TTP)?
1) Immune: Idiopathic (def. ADAMTS13 = cannot cleave vWF) or secondary to autoimmunity
2) Secondary:
- Malignancy related (TMA)
- DRUGS: Ticlopidine, Cyclosporine A, Clopidogrel…etc
- HSCT rejection
What nutrient def. can cause hypoproliferative anaemia?
- Iron deficiency 2. Vitamin B12 / folate deficiency
Which primary BM pathologies can cause hypoproliferative anaemia by infiltration?
- MDS
- Leukaemia
- Lymphoma
- Myeloma
(myeloproliferative neoplasm (e.g. polycythemia vera): INCREASES hematopoiesis )
List 2 primary BM failures causing pancytopenia?
- Aplastic anaemia (autoimmune)
2. inherited bone marrow failure syndromes (IBMFS)
Which blood metric is critical to determine hyper vs hypoproliferative anaemia?
Peripheral blood film examination with estimation of reticulocyte count***
Low = can indicate BM failure/ nutrient def.
Which 4 serum molecules indicate haemolysis?
- Increased total bilirubin
- Increase LDH
- Decrease Haptoglobin
- Decrease Methemalbumin
Why is Haptoglobin and methemalbumin decreased due to haemolysis?
- Haptoglobin take up Hb to form complex»_space; cannot pass renal glomeruli»_space; prevent excretion
- Methemalbumin bind to Hb after Haptoglobin is used up
List 3 lab tests to further ddx haemolysis cause?
Blood film/PBS (red cell morphology: e.g. spherocytosis fragmentation, signs of oxidative hemolysis)
Direct, indirect antiglobulin tests
G6PD assay
List the most common causes of warm and cold immune haemolysis?
Cold: infections
Warm: autoimmune disease, drugs
Both: idiopathic or part of LPD
Give 4 principle causes of bleeding tendencies?
Clotting factor deficiency– coagulopathy, hemophilia A/B
Platelet – quantitative / qualitative functional disorders
Drugs: functional disorder: warfarin, factor inhibitors…
Connective tissue / collagen vascular disease
What tests should be done to ddx platelet or coagulation disorders?
PBS/Blood film
Clotting profile: PT, APTT, TT
Other ancillary investigations (e.g. VWF ristocetin cofactor assay)
List some causes of isolated thrombocytopenia?
1) Primary BM failure (rare to just involve one lineage, except congenital amegakaryocytic thrombocytopenia)
2) Peripheral causes:
- Immune mediated destruction: Autoimmune Thrombocytic Purpura + Alloimmune Thrombcytopenia
- Non-immune: increased sequestration or consumption (DIC, TMA, TTP)
- Drug induced
List some causes of thrombocytopenia asso with other cytopenias?
Peripheral:
- Hypersplenism (sequestration and consumption)
- Autoimmunity against HSC (e.g Aplastic anemia)
Primary:
- BM pathology (infiltration, e.g. leukemia, lymphoma)
- Primary BM failure
List clonal or reactive causes of high WBC count in peripheral blood?
Clonal:
- Blasts >=20%: acute myeloid leukemia, acute lymphoblastic leukemia
- Blasts <20%: other myeloid malignancies: MPN, MDS
Reactive:
- Infection
- Inflammatory/autoimmune
- Paraneoplastic/ solid tumour reaction
Which types of acute leukemia doesnt present with Blasts >=20%?
- Acute promyelocytic leukemia
- Acute myeloid leukemia with t(8;21) translocation
- Acute myeloid leukemia with t(16;16) translocation
Characteristic genetic mutation of APL?
t(15;17) PML-RARA
Describe the morphology of WBC in APL?
Abnormal promyelocyte (Faggot cells: bilobed nuclei, Auer rods, abundant malignancy features)
– no need to see >20% blasts to dx
Treatment regimen for APL?
ATRA/ Arsenic trioxide immediately +/- supportive transfusion, esp. platelet, plasma
+ Correct coagulopathy, thrombocytopenia (DIC, restore platelet)
+ Treat any underlying infection
+ Treat and prevent tumor lysis syndrome (TLS) e.g. xanthine oxidase
Which procedures must not be done for APL?
Do not perform invasive procedures
Do not give granulocyte colony stimulating factor (G-CSF)
Do not stop ATRA/ATO
Which lab tests for Dx of APL?
Bone marrow examination with cytogenetics
Molecular genetics (e.g. RT-PCR for PML-RaRα)
PBS: Faggot cells and Auer rods
List some ADR of ATRA/ATO for APL treatment?
General:
Skin rash Headache Nausea, vomiting
ATO specific:
Hepatitis
Prolonged QTc = arrhythmia
Risk of herpes zoster reactivation
MCV of Inherited sideroblastic anaemia?
Microcytic
occasionally acquired due to nutritional deficiency
Define the stain used to ID sideroblastic anaemia, histological and marrow appearance?
- Iron stain >1/3 of erythrocyte: Dysplastic with cytoplasmic vacuoles in erythroid and myeloid precursors
- Hypercellular marrow with Nucleus-cytoplasmic asynchrony
List 2 inherited membranopathies that cause haemolytic anaemia?
Her. elliptocytosis
Her. Spherocytosis
Describe the absorption of copper and its function?
Dietary copper absorbed at small bowel
Transport in plasma by albumin/ Transcuperin to liver
Biliary excretion or carried by Ceruloplasmin to tissue
> co-factor for metabolism, incl: erythropoiesis and heme synthesis
List 1 acquried and 4 reversible causes of sideroblastic anaemia?
Acquired = MDS
Reversible: Alcoholism Drugs (e.g. isoniazid) **Copper deficiency** **Pyridoxine def.**
3 mechanisms of bleeding in APL?
- Marrow infiltration»_space; reduced platelet production
- Increased consumption of plt due to DIC
- Hyperfibrinolysis due to increased Annexin II»_space; deplete fibrinogen
List some plasma markers of hypercoagulation?
Increased:
- Prothrombin
- D-dimer
- Thrombin- Antithrombin complexes (TAT)
- Fibrinopeptide A (FPA)
List some plasma markers of fibrinolysis ?
- Low plasminogen, a2-antiplasmin, fibrinogen
- ## Increased D-dimer, Fibrin degradation products (FDP)
APL usually presents with leucocytosis. T or F?
False
Only 10% APL = high WBC at presentation
Usually leukopenia
