Heamatology Flashcards

Question

Transferrin

Answer 1

Binding protein and part of innate immune system Decreased in inflammatory states May rise in response to iron deficiency state Transferrin saturation - If less than 20% there is iron deficiency state, if over 45% there is iron overload state

Answer 2

Decreased production - BM suppression due to alcohol, chemo, myelofibrosis, virus, nutritional deficiency, liver disease Pseudothrobocytopaenia - improper sampling and clumping Dilution - MBT, massive resus Increased destruction SLE, ITP. DIC, drugs, TTP, APLS, HELLP, circuits Sequestration - hypersplenism, hepatic sequestration, extremes of temp

Answer 3

Minimise destruction - withhold heparin, manage sepsis, address specific aetiologies (TTP, HELLP) Maximise production - Nutrition, rationalise drugs that are BM toxic, correct BM failure if possible Protect from complications - Postpone non essential invasive procedures Cover essential procedures with platelets

Answer 4

occur after 2-3 weeks RBCs unergo a structural and function change Changes include - - reduced deformability - reduced 23DPG -> left shift and decreased O2 delivery - increased adhesiveness - decreased concentration of NO - reduced ATP - accumulation of pro-inflammaory bioactive substances

Answer 5

NEJM 2017 - transfusion of freshest blood vs standard care (mean 22 days) - no difference in death at 90 days or secondary outcomes - subgroup analysis - higher APACHE group had higher 90 day mortality with fresher blood Bottom line - no need to use newest blood, no harm from using older blood

Answer 6

Increased plasma cells - due to; plasma cell disorder - MM, Waldenstroms macroglobulinaemia, solitary plasmacytoma Other causes - pulmonary TB, cirrhosis, adenoCa of colon, syphillis

Answer 7

Often due to waldenstroms (IgM) but can be due to any plasmcytosis Clinical presentation - - severe headaches (due to increased ICP from venous occlusion) - fluctuating level of consciousness - stroke - seizures - coma - constitutional symptoms - fatigue, malaise, letheragy - haemorrhagic symptoms - epistaxis, mucosal bleeding - blurred vision (retinal vein occlusion) - renal failure - aggravated heart failure Lab - - leucocytosis (suggestive of malignancy) - high plasma count - high globulin level Mx - plasmaaphesesis

Answer 8

deformed lmyphocytes associated with CLL

Answer 9

inflammation -> cytokine release -> increase hepcidin -> reduced iron release from BM and macrophages and reduced absorption of iron

Answer 10

``` Low MCV low iron low ferritin (only cause) high transferrin (a binding protein - increases as a reaction) tranferrin saturation <<20% ```

Answer 11

``` may be microcytic or normocytic low iron normal ferritin low transferrin normal transferrin saturation ```

Answer 12

acute phase protein pregnancy malignancy iron overload chronically transfused states - sickle cell chronic inflammatory states - chronic liver/renal disease, HIV haemophagocytic lymthohistiocytosis - causes a VERY high ferritin - may be congenital or acquired; infection (|eBV, CV, HIV), neoplastic (lymphoma), autoimmune (SLE)

Answer 13

AML - - acute proliferation of immature myeloid precursor cells - acute promyelocytic anaemia is characterised by dense cytoplasmic granules and Auer rods ALL - childhood, good prognosis CLL - - presents with B symptoms, BM failure, splenomegaly and autoimmune haemolytic anamia - richters transformation -> diffuse large B cell lymphoma associated with poor prognosis CML - linked to philadelphia chromosome - typically beings with chronic phase -> accelerated phase -> blast crisis - presents with wt loss, splenomegaly, fever, night sweats

Answer 14

Hodkins - seen in young - reed-sternberg cells are characteristic on hisology Non-hodgkins - - heterogeneous group with 30 different subtypes - may be low grade or high grade Low - follicular (most common), waldenstrom macroglobulinaema, mantle cell lymphoma High - most common is diffuse b cell lymphoma - Burkitts - fast growing, high risk of TLS

Answer 15

plasma cell malignancy | present with bone pain, fractures, BM faliure, renal failure

Answer 16

Source of stem cells - - peripheral - bone marrow - umbilical cord blood Donor of cells - - autologous - re-infusing peripheral blood of patient from during time of remission - allogenic - donor; more intensive myeloablative regimens and immunosuppresion

Answer 17

Pre-engraftment - <30days - at risk of bacterial infections due to neutropenia Early post-engraftment - 30-100days - cell mediated immunity impaired - risk of fungal and viral infections (CMV, PJP, aspergillus) Late post-engraftment - - impaired reticuloendothelial, cell medicated and humoral factors - at risk of mycobacteria and viruses

Answer 18

``` INfection GVHD Graft failure Diffuse alveolar haemorrhage Idiopathic pneumonia syndrome Engraftment syndrome cryptogenic organising pneumonia veno-occlusive disease Posterior reversible encephalopathy syndrome post transplant lymphoproliferative disorder TTP ```

Answer 19

incidence 30-50% post allogenic Tx - increases with advancing age of donor and recipient, inadequate immunosuppresion, HLA mismatch, use of peripheral blood as stem cell source Acute - presents 7-28days after Tx with rash (esp on palms and soles), dirrhoea and intrahepatic cholestasis Is staged and graded - - each system staged 0-4 - then combined to give clinical grade Prophylaxis is with immunosuppressants treatment is high dose methyl pred

Answer 20

multi-organ syndrome which occurs >100 days after Tx May be limited or extensive Can involve - skin, eyes, lungs, salivary glands, neuromuscular system, liver Treatment is difficult as need to increase immunosuppresion but try to avoid infections

Answer 21

usually seen 3/52 after Tx diffuse infiltrates on CXR high mortality

Answer 22

also known as capillary leak syndrome - presents 4-5 days after autologous Tx with fever, rash, non-cardiac pulm oedema Use of GCSF increases prevalence and must be stopped

Answer 23

occurs 1-3/12 after Tx Presents with SOB, fever, cough Treatment is with steroids and response usually good Other causes - - follow on from many types of pneumonia - drugs - connective tissue disordrs - organ tx (BM and lung) - malignancies - radiotherapy Is an important cause of peripheral consolidation on HRCT - presents with flu-like illness Definitive Dx is with lung biopsy and negative mirco - PFT will show reduced DLCO NB - it is DIFFERENT to bronchiolitis obliterans - non reversible due to fibrosis and inflammation

Answer 24

Triad of - - painful hepatomegaly - jaundice - ascites Presents 3/52 after Tx Other features - wt gain, encephalopathy, bleedings, hepato-renal sydrome Doppler will show reduced or reversed portal flow

Answer 25

Characterised by headache, seizures, visual loss T2 MRI (CSF bright) shows diffuse hyperintensity in parieto-occipital white matter

Answer 26

Neutropenic sepsis - Abx in1 hours, consider antigungals if no improvement in 4-7days - start with anti-pseudomonal beta-lactam with addition of vanc/aminoglycoside or fluroquinolone if resistance suspected ``` Neutropenic enterocolitis (typhlitis) - abdo pain, fever and diarrhoea due to mucosal wall damage - usually needs conservative Mx (TPN) ``` Respiratory failure - many causes AKI - many causes TLS

Answer 27

Non infectious - general - ARDS - aspiration - pulmonary oedema - chemo-induced toxicity - cryptogenic organising pneumonia - pulmonary infiltration - leukaemia or thumour Non infectious specific to HSCT - - diffuse alveolar haemorrahge - idiopathic pnemonia syndrome - engraftment syndrome Infectious - - bacterial - psuedomonas, klebsiella, acinetobacter, staph, enterococcus, strep, leigonella, mycoplasma - viral - flu, adenovirus, parainfluenza, RSV, CMV, HSV, VZV - fungal - candida, aspergillus, PJP - mycobacterium - TB

Answer 28

oncological emergency caused by rapid lysis on tumour cells -> release of intracellular contents into circulation Characterised by - raised K, PO4, urate, LDH low Ca Increased risk with - (can be divided into patient and tumour factors) - large tumour mass - organ infiltration by tumour - bone marrow involvement - pre-existing renal disease or dehydration - tumours sensitivity to chemo - high intensitiy of chemo - acidic urine - nephrotoxin exposure - unchecked K and PO4 replacement - pre-exisiting gout

Answer 29

Prevention - Hydration to achieve u/o 1-1.5ml/kg/hr to reduce chance of uric acid precipitating in renal tubules Avoid K containing fluids Allopurinol - 300-600mg/day - decreases uric acid formation by blocking xanthine oxidase enzyme Rasburicase - a recombinant urate oxidase enzyme that converts uric acid to allantoin (10x more soluble that uric acid) Alkalinization of urine - not common - aim is to reduce the liklihood of uric acid precipitating in the tubules

Answer 30

repeated dose of rasburicase Careful management of fluids and electrolyes Specific Mx of hyperK, HypoCa and hyper PO4 Haemodilysis for standard indications

Answer 31

``` malaria myelofibrosis sarcoidosis amyloidosis CML chronic liver disease kala-azar (viscaeral leischmaniasis) ``` the above list also cause massive splenomegaly ``` pernicious anamia acromegaly thyrotoxicosis SLE obesity viral infections eg EBV metabolic storage diseases ```

Answer 32

``` malaria myelofobrosis sarcoid amyloid CML chronic TB thalassaemia major polycythehmia Waldenstroms macrogolobulinaemia ```

Answer 33

vWB disease platelet dysfunctoin fibrinolysis disorder SHould order platelet function studies

Answer 34

Exrinsic pathway failure warfarin vit K def liver diease isolated factor VII def

Answer 35

Intrinsic pathway failure ?factor deficiency or anticoagulant factor - answered by mixing studies factor deficiency fixes with mixing - vWB disease - de factro factor 8 deficiency - factor 8 (haemophilia A) - factor 9 (haem B) - factor 11 (hame C - 8% ashkenazi jews) - factor 12 - very rare Doesnt fix; presence of anticoagulant factor - NOrmal TT and RT - antiphospholipid antiodies High TT, normal RT -heparin High TT, high RT -low fibrinogen, abnormal fibrinogen, amyloid

Answer 36

``` antithrombin protein c protein s factor 5 leiden lupus anticoagulant - antiphospholipid syndrome anti Beta 2 glycoprotein antibody (APS) anticardiolipin antibody (APS) prothrombin gene mutation ```

Answer 37

consequences are thrombosis and loss of heparin effect management is supplementation of ATIII with purified factor or FFP Causes - inherited ATIII defects Acquired - - reduced production - liver disease, oral contraceptive, eclampsia - loss of protein - nephrotic syndrome, plasmapheresis with albumin, extnesive blood loss - increased consumption - DIC, acute thrombosis, extra-corporeal circuits

Answer 38

R value = reaction time (s); time of latency from start of test to initial fibrin formation (amplitude of 2mm); i.e. initiation K = kinetics (s); time taken to achieve a certain level of clot strength (amplitude of 20mm); i.e. amplification alpha = angle (slope between R and K); measures the speed at which fibrin build up and cross linking takes place, hence assesses the rate of clot formation; i.e. thrombin burst TMA = time to maximum amplitude(s) MA = maximum amplitude (mm); represents the ultimate strength of the fibrin clot; i.e. overall stability of the clot A30 or LY30 = amplitude at 30 minutes; percentage decrease in amplitude at 30 minutes post-MA and gives measure of degree of fibrinolysis CLT = clot lysis time (s)

Answer 39

Increased R time => FFP Decreased angle => cryopreciptate Decreased MA => platelets (consider DDAVP) Fibrinolysis => tranexamic acid (or aprotinin or aminocaproic acid)

Answer 40

heterogeneous mix of mucopolysaccharides subcut dose take 1-2hours to reach peak effect Mechanism - - enhances activity of ATIII by factor of 1000 - ATIII inactivates several factors - Xa and thrombin LMWH vs UFH - - inactivation of thrombin depends on heparin molecule lenght - clexane does not affect it - inactivation of Xa is independent of length so both effect it

Answer 41

potentiated by - - sodium valproate - hyroxycholoroquine Effects of heparin antagonised by - - antihistamines - digoxin - nicotine - tetracyclines

Answer 42

HITS - occurs 5-10days after start of heparin - mostly associated with UFH, more frequent in elderly - type 1 - mild, reversed by cessation of heparin, occurs in 10% patients - type 2 - severe, associted with thrombosis in 30% cases, due to formation of antibodies to the complex made up of platelet factor 4 (PF4) and heparin osteopaenia mineralocorticoid alopecia elevation of AST and ALT

Answer 43

1mg reverses 100units given slowly Side effects - - catastrophic hypotension due to vasodilatation - pulmonary hypertension - anaphylaxis

Answer 44

due to - - increased heparin-binding protein levels (all of them are acute phase reactants) - low antithrombin III levels - increased heparin clearance - high factor VII levels Management - - change to LMWH - give FFP or cryo - given ATIII concentrate

Answer 45

reversible inhibition of P2Y12 ADP receptor -> inhibition of cAMP dependent platelet activation Biliary clearane duration of action 3-5 days

Answer 46

``` Dabigatran - direct thrombin inhibitor - renally excreted can use dialysis to clear lower bleeding risk than warfarin new antidote - praxbind (monoclonal antibody) ``` Rivaroxiban - - factor Xa inhibitor - prevents thrombin generation - bad in both liver and kidney disease - not able to dialyse

Answer 47

``` ca channel blockers fluconazole immunosuppresants macrolides (clarithro, erythro) amioderone tamoxifen ```

Answer 48

Absolute contraindication to anticoagulation in patient with high risk DVT/PE COmplication of anticoag -> needs to be reversed Inability to achieve full anticoagulation PE while fully anticoagulated Extended indications - no evidence, but may get placed -- trauma, burns, cancer pt, clot induced pulmoary HTN

Answer 49

modulates; B and T cells, macrophages, cytokines networks and complement Regulates cell growth

Answer 50

Haematological - idiopathic thrombocytopenic purpura (ITP) - post plasma exchange course completion - antiphospholipid syndrome (APLS) - chronic graft versus host disease (hypogammaglobulinaemia) Infections - toxic shock syndromes (staphyloccocal and streptococcal) Vasculidities - Kawasaki disease - Wegener’s granulomatosis - Microscopic polyangiitis Dermatological - pemphigus vulgaris - bullous pemphigoid - SJS/TEN (controversial) Neuromuscular - GBS (AIDP) - dermatomyositis - myasthenia gravis - chronic inflammatory demyelinating peripheral neuropathy (CIDP) - Eaton-Lambert syndrome - Stiff Person Syndrome - Multiple sclerosis Renal transplant rejection (controversial)