Haematology and Oncology Flashcards

Question

Management of Tumour Lysis Syndrome

Answer 1

*Hydration and diuresis - to maintain volume and enhance renal clearance of K/PO4/Urate *Rasburicase = recombinant urate oxidase to enhance degradation of urate to allantonin which is more soluble and renally excreted *Treat electrolyte abnormalities e.g hyperkalaemia and symptomatic hypocalcaemia *Haemodialysis, for standard indications; severe electrolyte abnormalities, oliguria, fluid overload, acidosis.

Answer 2

*Viscoelastic tests are POC tests of whole blood clotting *Blood is added to cuvette ( cup) with suspended pin at 37degrees *TF / kaolin added *Rotation motion occurs and the resistance developing to rotation measured and displayed graphically *In TEG the cup spins ( T - cup) *In ROTEM the pin spins

Answer 3

*Trauma *Post cardiac surgery *Post liver transplant *To guide massive transfusion *DIC *Peripartum period

Answer 4

R time *Reaction time - time from latency to initial fibrin clot formation *dependant on CF K time: *time from end of R to certain fibrin clot strength *dependant on fibrinogen alpha angle: *rate of fibrin clot strength *dependant on fibrinogen Max amplitude: *Peak clot strength *80 % dependant on platelets, 20% on fibrinogen LY30: *percentage decrease from MA after 30 mins *correlates to rate of fibrinolysis

Answer 5

Prolonged R time = deficient CF = give FFP Prolonged K time = deficient fibrinogen = give cryo Decreased alpha angle = deficient fibrinogen = give cryo Decreased MA = decreased overall clot strength = give platelets or DDAVP Decreased Lysis 30 time = enhanced fibrinolysis = need TXA

Answer 6

Advantages: POCT Tests whole blood coagulation Real time evaluation of clot formation Can test fibrinolysis - which normal coags cant Predictor of post operative hypercoagulation states Quick than full coagulation test May guide balanced transfusion Reduces products in e.g. cardiac surgery Sensitive to heparin effect Disadvantages: Requires user training Machine recalibration is needed frequently Doesn't measure effects of hypothermia

Answer 7

INTEM: Measures intrinsic pathway (APTT), phospholipid added EXTEM: Measures extrinsic pathway (PT), TF added FIBTEM: Measures fibrinogen function by using platelet inhibitor to block the platelet contribution to clotting APTEM: uses aprotinin to inhibit fibrinolytic proteins. It is otherwise identical to EXTEM. A shortened CT (R time) and a higher MCF in an APTEM test ( c/w) EXTEM) suggest that hyperfibrinolysis is taking place. Additional: HEPTEM: heparinase added to sample - removes effect of heparin. A significantly shortened HEPTEM time c/o INTEM would suggest presence of heparin e.g. in CPB ECATEM: Ecarin is a prothrombin ( FII) activator. In the presence of direct thrombin inhibitors the ECATEM will be prolonged

Answer 8

HIT 1: *benign *non immune *mild aggregation resulting from PF4/heparin complexes *mild thrombocytopenia ~ plt count 100 *self limiting on cessation of heparin *up to ~ 10% of patients on heparin *no associated thrombosis HITT 2 ( thrombosis and thrombocytopenia) *life threatening *IgG mediated antibodies to PF4/Heparin complex *subsequent thromboycytopenia ( macrophage mediated) *thrombosis and consumptive thrombocytopenia from activation and aggregation *incidence higher with UFH > LMWH *requires anticoagulation

Answer 9

IgG mediated response to PF4/Heparin complexes "Anti PF4 antibodies" IgG coated platelets taken up by macrophages = thrombocytopenia Abnormal platelet activation and aggregation = arterial and venous thrombosis Anaphylactoid reactions can occur to heparin due to Ab presence

Answer 10

R/F = cancer, trauma and surgery (increase PF4 release) 4T score: - Thrombocytopenia severity - Timing - day 5-10 most common, unless prior exposure to heparin - Thrombosis presence - Thrombocytopenia possibly due to other causes?

Answer 11

NB Weak evidence base: -recurrent PE on full anticoagulation - patients with absolute CI to anticoagulation ( e.g. SAH with unsecure aneurysm or HITTS (II) unable to use alternative agent) -Life threatening proximal DVT (e.g ileofemoral) despite anticoagulation -high risk trauma patients: ( TBI / Spinal / Pelvic #)

Answer 12

Advantages: - May decrease r/o of fatal PE in patients with HIGH risk DVT e.g. proximal iliofemoral even on anticoagulation = Can be used to reduce r/o PE in patients with absolute contraindication to anticoagulation - Newer devices are removable Disadvantages: - Weak evidence base for their use - Insertion complications - failure / vessel injury/ perforation / air embolus - Delayed complications - infection / IVC clot with thrombosis -> venous stasis, IVC can occlude ( 20% patients at 5 years), device # and displacement risks - IVC filters don’t prevent new DVT formation

Answer 13

Platelet < 150 1) Pseudothrombocytopenia - clumping 2) Dilution: - Massive transfusion (also causes platelet consumption) -Fluid resuscitation 3) Reduced Production ( BM suppression or infiltration) -Drugs e.g. linezolid / valproate -Viral infection -Liver disease (reduced thrombopoeitin) -B12 / folate deficiency -Haematological malignancy 4) Increased destruction: -Drugs - heparin / antiplatelets -Sepsis -DIC - Immune - ITP -TTP -HUS / HELLP -Haemolysis ( MAHA) -Intravascular circuit loss - CBP / ECMO / Dialysis / IABP 5. Sequestration: -splenomegaly - e.g. malaria and other causes 6. increased aggregation - sepsis -MODS -Massive PE

Answer 14

General approach to likely cause involves history, examination and investigation: Basic bloods: 1) blood film - clumping / spherocytes / signs of infiltration 2) LFTS - liver disease causing dec thrombopoietin? 3) B12 / Folate 4) Haemolytic screen 5) Coags - ?DIC Infection screen: 1) Viral - EBV / CMV/ Malaria if splenomegaly / HIV / Hepatitis 2) Septic screen Disorder specific: 1) Vasculitis screen 2) ADAMST13 activity - for TTP 3) ELISA Test for PF4 antibody - HITTS 4. BM aspirate: malignancy / aplastic anaemia

Answer 15

ECHIS is a snake venom added to blood sample which activates prothrombin without requiring vitamin K. If PT prolonged but ECHIS time normal = Vit K deficiency or warfarin use If ECHIS time and PT prolonged then liver dysfunction present (ie factor deficient)

Answer 16

HITT screen performed if preprobability (4T score) is high (4 or more) for HITTS. Test is an immunoassay for anti PF4 antibodies. Sensitive but not specific Don't perform if pre test probability is low NB gold standard test for HITTS is a functional assay if the pre test probability was high and the screen is equivocal.

Answer 17

* V2 vascular endothelial release of Vwf and FVIII enhanced * Increases the density of platelet surface glycoprotein receptors * Enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na+/Ca2+ mobilisation. * Thus, increases platelet aggregation It is not a blood product, and can be used in bleeding Jehovah's witnesses

Answer 18

*most common inherited bleeding disorder ( 1-2% prevalence) *Autosomal dominant *results in abnormal platelet adhesion and prolonged bleeding time Types: 1) mild form, reduced vWF levels ( ~ 90% cases) 2) dysfunctional vWF -> DDAVP is CI 3) absent vWF -> most severe form Ix: Plt count will be normal Prolonged bleeding time APTT might be slightly prolonged ( due to decreased FVIII) vWF level and FVIII level correlate with disease severity Mx: -DDAVP if patient is DDAVP responder ( as prophylaxis 0.3mcg/kg) -Consider Replacement therapy with FVIII or vWF -Consider cryo as source of vWF is acute bleeding -avoid antiplatelets

Answer 19

MCV>100 *alcoholism *B12/folate def *myelodysplastic syndromes *chronic liver diseases *hypothyroid *chemo / valproate / trimethoprim / metformin

Answer 20

Rouleaux are stacks of RBC which abnormally aggregate together Causes are anything which increases your ESR -> Infection / dehydration/malignancy e.g. multiple myeloma

Answer 21

Howell Jolly bodies are bits of DNA left over in RBC They are seen post splenectomy or in functional asplenia Also associated with steroid use and in macrocytosis of any cause

Answer 22

Heinz bodies are bits of denatured Hb within RBCS Indicate oxidative stress Either disorders of RBC metabolism or haemaglobinopathies 1) Drugs causing oxidative stress -> quinidine, primaquine 2) Disorders of metabolism -> dapsone / bactrim G6PD deficiency 3) Abnormal Hb's - alpha thalasaemia, methylene blue metHb 4) Post splenectomy - no spleen to recognise and remove abnormal RBC

Answer 23

Pappenhimer bodies = iron graunles in sideroblastic anaemias (disorders of iron utilisation) Blister cells indicate oxidative stress similar to Heinz bodies and are seen in G6PD deficiency or in dapsone or primaquine toxicity Basophilic stippling is suggestive of lead poisoning

Answer 24

Polychromatic RBC are cells which stain blue/grey due to having left over bits of genetic RNA PO4 groups in them Represents either increased bone marrow stress or a failure of normal regulatory mechanisms responsible for "quality control" of RBC e.g. post spenectomy

Answer 25

Boosters every 5 years: Pneumococcal Hib Men C Influenza

Answer 26

Encapsulated organisms are the biggest risk to post splenectomy patients - the spleen normally removes these -strep pneumo -haemophillus influenzae -neiserria meningitidis -capnocytophagia - GNB from dogs/ cats -malaria -babeosis ( from ticks) -

Answer 27

Howell Jolly bodies - DNA fragments Heinz Bodies - denatured Hb - oxidative stress Thrombocytosis Target cells - excess RBC membrane Acanthocytosis -> spiky RBCS Anisocytosis - variation in RBC size

Answer 28

This refers to the presence of immature granulocytes ( neutrophils) and nucleated immature RBC on a blood film Suggests bone marrow activation/stimulation The possible causes are: - BM infiltration = leukaemia / myelofibrosis / solid tumour infiltration eg. breast cancer - BM excess activity = sepsis, severe haemorrhage or haemolysis, marrow recovery following suppression, Inflammatory conditions ( e.g autoimmune conditions)

Answer 29

Toxic changes refers to presence of immature neutrophils Includes at least 2 of the following: Toxic granulocytosis - immature neutrophils Toxic vacuolation - indicates phagocytosis Dohle bodies - remnants of Rough ER These are all evidence in severe inflammatory states e.g. infection

Answer 30

Band forms are immature neutrophils If there is > 5% band forms on a blood film this is a left shift

Answer 31

Left shift = * immature > mature cells. * There is a higher number of band forms (aka. immature neutrophils) *Causes of Left shift: * Sepsis * Haemorrhage - due to adrenergic mobilisation of marrow neutrophils * Necrosis - of any sort * Bone marrow infiltration * Anaemia - in an exaggerated haemopoietic reaction the BM releases a lot of immature cells which include immature neutrophils.

Answer 32

This is the presence of vacuoles in neutrophils, indicative of phagocytosis and is representative of severe infection e.g bactaraemia ( Part of toxic changes on blood film along with Dohle bodies and toxic granulation neutrophils)

Answer 33

*Leukemoid reaction refers to transient rise in WCC count ( typically neutrophilia but can also have lymphocytosis) *WCC ~ 50,000 *WCC counts higher than this may represent leukaemia - esp myeloid leukaemia *Immature neutrophils seen - band forms with left shift *Toxic changes present on blood film - neutrophil granulocytes, vacuolation and dohle bodies *Seen mainly in severe infection and ischaemia - e.g. ischaemic colitis or hepatic necrosis or malignancy. *Should get better with treating underlying condition

Answer 34

Plasma cells are derived from B lymphocytes and present in BM - secret antibodies Plasmacytosis causes grouped into haematological causes or infective causes: PLASMA CELLS Haem causes: -Multiple myeloma - B cell lymphoma - Plasmocytoma - Spherocytosis - Serum sickness - Plasma cell leukaemia - MGUS - Waldenström macroglobulinemia Infectious causes: - Varicella zoster - Leprosy - TB - Hepatitis / HIV

Answer 35

-A haem emergency which usually results from increased circulating serum immunoglobulins Examples: * Multiple myeloma *** Waldenstoms macroglobinaemia - excess of IgM ( most hyperviscous as IgM is massive)*** * Leukaemias * Polycythaemia rubra vera Rx: urgent plasmapheresis

Answer 36

Smudge cells are deformed lymphocytes seen in CLL

Answer 37

HLH represents a hyperimmune state and may be underdiagnosed in ICU It may be inherited or acquired Pathophysiology: *uncontrolled macrophage and T-cell activation from cytokine production *may be triggered by infection / malignancy or rhem disease e.g. SLE Diagnosis: Either by molecular diagnosis or by clinical criteria (should have 5 of 8): * Fever * Splenomegaly * Cytopenia of two or more cell lines (i.e. Hb <90 plt <100, Ne <1 x 10E3/L) * Either elevated triglycerides or low fibrinogen * BM evidence of haemophagocytosis * Serum ferritin > 500 mcg/mL (much higher) * Low or absent NK cell activity (by flow cytometry, if available) * Soluble CD25 > 2400 U/mL Ferritin usually > 10,000 Management: Treat cause Chemotherapy may be required in severe cases Supportive care - i.e. transfusions / PJP and fungal prophylaxis

Answer 38

Requirement = 10mg/day Iron in the body: * Stored in Hb >70% * Stored in myoglobin > 5% * Stored as ferritin ~ 20% * Circulating bound to transferrin Physiology: * Absorbed at small bowel ( duodenum) * Ferrous Fe 2+ is soluble * Ferric Fe3+ insoluble -> HCL helps facilitate conversion to Fe2+ for absorption * Once in enterocyte bound to ferritin * Carried in the blood bound to transferrin -> to BM to be used in Haem synthesis, or to liver to be stored as ferritin

Answer 39

Ferritin is the gold standard marker of iron stores Found in all cells -> most in liver / reticuloendothelial cells Small amount of ferritin in plasma is proportional to body iron stores. Normal = 15 – 300 ug/l ↓ ferritin = iron deficiency ↑ ferritin = inflammation (sepsis / kidney / liver disease), malignancy, pregnancy, chronically transfused patients ( e.g sickle cell) ↑↑↑ = HLH

Answer 40

Transferrin carries iron in the plasma Total iron binding capacity (TIBC) is an alternative to measuring Transferrin - being a direct measure of level of transferrin. transferring = inflammatory states / malnutrition / liver disease ↑transferrin = iron deficiency

Answer 41

%Transferrin saturation - is the % of transferrin which is saturated with iron. Normal is ~ 20-45% Low % Tsat < 20% = iron deficiency High % Tsat > 45-50% = indicative of iron overload = Haemochromatosis or recent transfusion

Answer 42

*Eosinophils - (a type of granulocyte) - other granulocytes = basophils / monocytes and neutrophils * Allergy * Addisons * parasitic infections * sarcoidosis * leukaemia * lymphoma * melanoma * irradiation Eosinophilia also seen in convalescence from infection

Answer 43

PANCYTOPAENIA = reduction in all cell lines *Either due to BM failure (reduced production or infiltration) or peripheral cell destruction: Reduced Marrow Production: * Malignant infiltration * Drug Reaction (chloramphenicol, sulphonamides, phenytoin, carbamazepine, gold) * B12 deficiency * SLE * Myelofibrosis * Cytototoxic agents * Overwhelming infections Increased Peripheral Cellular Destruction: * SLE * HIV infection * Hypersplenism * paroxysmal nocturnal haemoglobinuria

Answer 44

Polycythaemia = Hb > 160 May be primary or secondary or relative Primary = Polychythaemia rubra vera Secondary = chronic hypoxia ( e.g. OSA/RHF), EPO injection or EPO secreting tumour, congenital cyanotic heart disease Relative = dehydration - diuretics / burns Clinical Features: Fundal hyperviscocity / headaches/ APO, thrombosis, /hyperviscocity, HTN, PVD/ splenomegaly/ plethora / pruritis/ gout Ix: Hb > 160, HCT raised In polycythaemia rubra vera - > increased WCC and platelets, microcytosis and slight anisocytosis (= variation in cell size) JAK2 mutation found in >95% pts with polycythaemia rubra vera

Answer 45

Risk Factors: *UL DVT associated with venous catheter placement -> -subclavian vein > IJV -catheter migration -increased number of lumens/size of catheter -blocked lines -irritant infusions -> TPN/Chemo UL DVT associated with underlying disease -> -Thrombophilia - > Protein C/S deficiency / Factor V Leiden / ATIII deficiency /antiphospholipid syndrome -malignancy -previous DVT -UL Trauma Features: -may be asymptomatic -pain / phlebitis / blocked venous catheter - Redness / swelling / paresthesia - signs of SVC obstruction Ix: Compression USS - >95% sensitivity and specificity. CT might be required to Dx SVC/ Intrathoracic DVT

Answer 46

Anaemia may be due to dilution, reduced production or increased loss of RBC Dilutional anaemia: *fluid replacement *incorrect sampling from IV line with running fluid Reduced production: *nutritional - > Fe deficiency / B12 / Folate deficiency *anaemia of inflammation -> cytokine mediated *reduced EPO production -> chronic renal disease Increased loss (Extravascular) *Bleeding - e.g trauma / GI loss *Iatrogenic - freuquent sampling / surgical blood loss Increased loss intravascular: *Haemolysis - autoimmune *Haemolysis - mechanical -> valve / ecmo or CRRT *Appropriate sequestering of abnormal Hb - sickle cell / thalassaemia *DIC

Answer 47

Anaemia of inflammation aka anaemic of chronic disease Low haemoglobin Low iron normal to high ferritin suppressed or normal erythropoietin elevated CRP Process is cytokine mediated (il-6) and involves increased hepcidin: * iron trapping - iron stores are 'normal' but unable to utilise iron for erythropoiesis * macrophage mediated RBC phagocytosis * directly induced BM suppression of erythropoiesis NB. in anaemia of chronic inflammation EPO may be normal or suppressed. Cytokine mediated direct suppression of erythropoiesis occurs independent of EPO

Answer 48

Haemophagocytic LymphoHistocytosis is a rare syndrome which can be congenital or acquired: Acquired causes: Infection - EBV,CMB, HIV, Leishmania (parasite) Malignancy - Lymphoma Inflammation - SLE Diagnosis = molecular diagnosis or fulfilling 5 of 8 clinical criteria: Criteria: * Fever * Splenomegaly * Cytopenia of two or more cell lines * Either elevated triglycerides or low fibrinogen * Histopathological evidence of hemophagocytosis (on BM, spleen or lymph node biopsy) * Serum ferritin > 500 mcg/mL (often much higher in HLH: ferritin > 3000 ng/mL is concerning for HLH and ferritin > 10 000 as highly suspicious (96% specific) * Low or absent NK cell activity (by flow cytometry, if available) * Soluble CD25 > 2400 U/mL

Answer 49

Rx aims to alleviate symptoms, reduce r/o PE and further DVT, and prevent post thrombotic syndrome. 1) Anti-coagulation: - Initial LWMH or UFH then... - either LMWH or oral anticoagulants for 3 - 6 months 2) Thrombolysis: - Limited evidence - Catheter-directed thrombolysis if upper limb has extensive swelling and functioned impairment 3. SVC filter: -No evidence base -Doesn't prevent new DVT -Only if absolute contraindication to anticoagulation and high risk of life threatening PE -associated high risks 4. Surgical thrombectomy if no other option available

Answer 50

DIC involves: Activation of coagulation by inflammation - > microthrombi form. * Cytokine release * Tissue factor (a potent procoagulant) is expressed on macrophages and monocytes * Endothelial dysfunction exposes more of the procoagulant surfaces behind the endothelium * Platelet activation and aggregation Consumptive coagulopathy -> leading to haemorrhage * Consumption of clotting factors * Consumptive thrombocytopenia Fibrinolysis and / or inhibition of fibrinolysis (which is mainly seen in septic DIC

Answer 51

DIC is an acquired syndrome characterised by the intravascular activation of coagulation with loss of localisation arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction Hemorrhage is often seen with DIC due to obstetric catastrophe or leukemia. Thrombosis is often seen with sepsis-associated DIC.

Answer 52

*Sepsis - Esp GNB, viral haemorrhagic fever, GAS *Obstetric catastrophes - (abruption, IUD, PPH, eclampsia, HELLP syndrome, amniotic embolism) *Trauma- (Severe tissue injury - Head injury, burns, fat embolism) *Major surgery *Pancreatitis, *Severe liver failure, toxicology (paracetamol OD) *Transfusion reactions *Snake venom

Answer 53

ISTH Scoring tool for DIC: -Components: INR, Fibrinogen, DDimer, Platelets -Score >5 = Overt DIC SIC score for sepsis induced coagulopathy - (SIC is a DIC which still hasn't had time to waste all your clotting factors, but which is already associated with the dysfunction of one or more organ systems) -Components: INR, platelets, SOFA score

Answer 54

VITT: RF: young, female, AstraZeneca and J+J Covid 19 Vaccines Pathophysiology: Antibodies form to the complex of PF4 platelet surface proteins and adenoviral RNA from the vaccine IgG mediated platelet activation and destruction Presentation: Hx + o/e: headache, visual change, features of CVST, PE, DVT, petechiae Ix: Falling plt count, Ddimer usually >4 times upper limit normal CT/USS: for thrombosis * PF4 ELISA normally used for “HIT” appears to detect the VITT antibody Management: Avoid repeat vaccination. Avoid Heparin due to overlap with HITTs Alternative anticoagulation - fondaparinaux IV immunoglobulin, 1-2g/kg over 2 days Plasmapheresis +/- high dose methylprednisolone if not improving or if thrombosis is severe and extensive

Answer 55

Haemolysis may be intravascular or extravascular. INTRAVASCULAR Immune: *ABO incompatibility or Rhesus mediated. *IgG warm AIHA - drugs (penicillin / ibuprofen / paracetamol), viral, CLL, Autoimmune - e.g. SLE/R.A *IgM cold AIHA -post viral, (mycoplasma / EBV / influenza), Paroxysmal cold haemolgobinuria Non-immune: *Mechanical - valves, ECMO, CRRT *Microangiopathic Haemolytic Anaemia - TTP/HUS/DIC *Severe sepsis - malaria, clostridium perfinigens *Heavy metals - e.g. lead/ mercury, copper poison EXTRAVASCULAR: RBC enzyme abnormalities: *G6PD deficiency (X-linked, African or Mediterranean descent, exposure to fava beans or drugs e.g. primaquine, nitrofurantoin). RBC membrane abnormalities *hereditary spherocytosis *paroxysmal nocturnal hemoglobinuria Hemoglobinopathies *sickle cell disease *thalassemia Hypersplenism of any cause

Answer 56

FBC and blood film LDH Reticulocytes count Haptoglobin Free Haemoglobin Indirect (unconjugated bilirubin) DAT - direct antiglobulin test - if positive = Warm AIHA

Answer 57

*ABO /Rhesus incompatibility *Warm IgG mediated AIHA - SLE/RA - Infectious -Drugs - penicillin, probencid, ibuprofen, paracetamol -CLL *Cold-IgM mediated AIHA -Post infectious -> EBV/CMV/Mycoplasma/Syphilis -Paroxysmal cold hemoglobinuria

Answer 58

RBC abnormalities: spherocytosis or fragmented RBCs, as well as pathognomonic erythrocytes such as sickle cells. High reticulocyte count ( a normal bone marrow responds to anaemia by ramping up the production of RBCs.) High LDH: An enzyme which leaks out of pretty much any damaged cells, and so is not specific for haemolysis Haptoglobin: the protein responsible for iron transport will usually be low when there is too much iron to transport. Free haemoglobin will be elevated as it spills out of RBCs. There may even be hemoglobinuria

Answer 59

When haemolysis is "warm", it is caused by antibodies maximally active at human body temperature, caused by IgG. DAT is positive for both IgG and complement C3d. Causes: *Infection *Drugs - penicillin, probenecid, mycophenolate, ibuprofen, paracetamol *Malignancy ->CLL, myeloma *SLE/RA/ Rx of warm haemolytic anaemia: - Corticosteroids are first-line treatment. - Splenectomy is the second-line treatment. (The spleen's macrophages are responsible for removing IgG-coated RBCs; also the spleen is a site of antibody production.) - Cyclophosphamide / azathioprine are reserved for those who fail steroids and splenectomy (or cannot have a splenectomy). IV immunoglobulin is not strongly indicated: some reports show benefit, others don't.

Answer 60

Warm AIHA = DAT +vE (IgG and Complement C3d) Rx: 1st Line = Steroids 2nd Line = Splenectomy Cyclophosphamide / Azothioprine for those who fail steroids.

Answer 61

G6PD is an enzyme found in RBC, providing reductive potential, as a source of NADPH in states of oxidative stress. G6PD is an x-lined recessive disorder, more commonly seen in males and in areas where malaria is prevalent - southeast Asia, Africa, parts of India and the Mediterranean. If there isn't enough G6PD there will not be enough NADPH with oxidative stress, resulting in RBC abnormalities including Heinz bodies (= bits of denatured Hb) This results in an acute haemolysis with certain triggers: Triggers: Foods - broad beans, blueberries Drugs: dapsone / co-trimoxazole, methylene blue, nitrofurantoin Infections DKA Management: Remove trigger. Supportive Consider transfusion of RBCs with normal levels of G6PD!

Answer 62

Massive splenomegaly: -CML -Myelofibrosis -Chronic Malaria -Visceral Leishmannia (Kala-Azar) -Sarcoidosis NB: Kala azar is the second largest parasitic killer in the world after Malaria.

Answer 63

APS consists of tendancy towards bleeding and to thrombosis. ***Sapporo Criteria:*** require at least 1 clinical and 1 laboratory feature: Clinical: -confirmed thrombosis -pregnancy morbidity e.g. recurrent miscarriage Lab: -Lupus anticoagulant -Anti-cardiolipin Ab,or Anti-B glycoprotein Ab ***Pathophysiology*** - autoantibodies to -ve charge phospholipid surfaces. - this reduces platelet aggregation and prolongs APTT. - Auto-antibodies also impair endothelial cell function leading to activation of complement and coagulation cascade.

Answer 64

Catastrophic APS affects <1% of people with APS. ***features:*** 1) History of APS or lab confirmation of lupus anticoagulant or Anti-cardiolipin/anti B-glycoprotein Abs 2) Acute < 1 /52 of onset 3) Severe,>3 organs involved 4) A / V thrombosis 5) Biopsy showing small vessel occlusion ***Presentation*** Neuro - CVST / Strokes Resp - PE / ARDS Renal - 70% have AKI, malignant HTN Skin - necrosis Lab -> APTT prolonged which doesn't correct with mixing studies, may have evidence of haemolysis, thrombocytopenia ***Management*** M - HR / BP, Temp, Spo2, RR, u/o, GCS E - likely critical care environment T - specific teams per organ involvement, haematology, critical care. ***Supportive care - *** ***Specific care:*** Anticoagulation and immunosuppression 1) LMWH -> Warfarin 2) Methyl pred 3/7 Second line - PLEX with FFP, IvIg may be considered.

Answer 65

***Vaso-occlusive crisis*** -assume this is the cause of any painful presentations -acute chest syndrome -> life-threatening lung infarction -> assume if hypoxia + chest pain ***acute splenic sequestration*** -typically occurs in infants - associated with increased spleen size - fall in Hb by >20 g/L, thrombocytopenia but normal or increased reticulocytes ***aplastic crisis*** - abrupt fall Hb as well as reticulocytes <1% - triggered by parvovirus infection

Answer 66

Veno occlusive Disease: May be mild -> rapidly fatal (in 40%) Pathogenesis -> thrombosis of the small central hepatic venules due to endothelial cell damage by high dose chemotherapy Presentation: During first 21 days following transplant, weight gain, painful hepatomegaly and jaundice. 50% go on to develop renal failure. Diagnostic Criteria: Seattle or Baltimore: Both need presentation <21/7 from BMT Investigations: transaminitis, hyperbilirubinaemia Doppler U/S showing reversal or diminished portal flow. management: -supportive, fluid restriction, diuresis, paracentesis - avoid infections and hepatotoxic medications - oral ursodeoxycholic acid (lowers bilirubin)

Answer 67

Philidelphia translocation is linked to CML CML usually presents with slow then rapidly progressive phase CML is a cause of massive splenomegaly

Answer 68

Hodgkin's Lymphoma: * Common in young people * Presents with cervical LN and B symptoms * Reed-Sternberg cells seen on biopsy * Chemo +/- radiotherapy * Curative in >75% patients

Answer 69

***CRAB:*** Calcium raised Renal impairment - due to free light chains / hypercalcaemia Anaemia - normochromic, normocytic Bony pain / lytic lesions

Answer 70

***Complications may be categorised as early -> late*** Early < 30/7 from BMT - PRE-ENGRAFTMENT Late > 100 /7 from BMT - POST ENGRAFTMENT ***Early pre engraftment:*** -neutropenic spesis -acute tumour lysis - rare - enteritis -veoocclusive disease of liver ( Liver pain, weight gain, 3 weeks post) - acute GVHD (allogenic HSCT) Also, graft failure ***Late post engraftment:*** -chronic GVHD Myopathy / neuropathy CMV - chronc second malignancies

Answer 71

Presents with triad of painful hepatomegaly, jaundice and ascites ( weight gain) ~ 3 weeks after a stem cell transplant Dx criteria: Seattle or Baltimore Mx: supportive + Defibrotide - an antithrombotic, anti-inflammatory

Answer 72

GVHD occurs with allogenic stem cell transplants Antigens on host cells are attacked by the donor T cells Biopsy of tissue / skin shows lymphocytic infiltration

Answer 73

Occurs with allogenic transplants RF: Unrelated donor/recipient Donor/recipient sex difference Older age > 40 recipient CMV +VE

Answer 74

aGVHD presents like a with: triad of system involvement: 1) skin - maculopapular rash 2) liver - jaundice, elevated bilirubin 3) GI - n+v, diarrhoea anorexia 50% of patients with aGVHD develop cGVHD. cGVHD presents like a new autoimmune condition: *absence of acute features Skin - sclerosis, nail changes, alopecia Ocular - chronic conjunctivitis GI: mucositis, oesophageal strictures MSK: Myositis May have pleural or pericardial effusions

Answer 75

Blood group describe the presence of antigens on RBCS Most common = ABO then Rhesus then others ( Kell, Duffy, Lewis etc.) ABO group * Carbohydrate antigens present on RBC and on the surface of tissue cells * Most common * Antigens = A or B, or both or none * IgM antibodies develop to foreign blood groups within 6/12 of life, usually due to environmental exposure * ABO incompatibility is a severe T1 hypersensitivity reaction Presence of blood groups in the population: * O group - 49% (universal donor blood as NO antigens) * A group - 38% * B - 10% * AB - 3% (Universal recipient = NO plasma antibodies) 85% of the population are Rh +ve

Answer 76

PRE-TRANSFUSION TESTING -group - for ABO / Rh -typing - for antibodies -cross match Involves: *meticulous attention to request form – INVALID if there is any discrepancy 1) group and hold/ type and screen: takes 45 min *ABO and Rh groups (forward and reverse typing tests) – takes 15 min 2) Antibody screen (for non-ABO Abs) – if found takes hours to resolve 3) Cross match (total 1-2 hours) *electronic cross match only if negative Ab screen (takes 1 hour total, including G&H) * serological cross match of patients plasma with donor cells if positive Ab screen (takes 2 hours total)

Answer 77

Forward grouping: patient RBCS mixed with known anti-A and anti-B antibodies. Reverse grouping: patient's plasma is mixed with known Type A or Type B red cells. Both must agree to formally identify the blood group

Answer 78

***RBC - *** 4 degrees, 35 days ***Platelets - *** 22 degrees, 7 days ***FFP /CRYO - *** - ve 25 for 12 months Nb Cryo is extracted from FFP ~ -6 degrees and contains fibrinogen, fibrinectin, vWF, FVIII and FXIII

Answer 79

* Anaemia and blood transfusion is common in the critically ill, and are associated with costs and morbidity/ mortality * Blood testing in the ICU is often excessive and unnecessary and contributes to increased costs and morbidity Strategies for blood conservation: Blood sampling * rationale approach to blood testing * closed system blood sampling (risk of arterial embolism) * use of point-of-care microsampling * use of small volume sampling devices Prevention and treatment of anaemia * use of appropriate transfusion triggers ○ - restrictive strategy Hb>70 for most patients Plt >50 less doing a procedure or bleeding * treatment of underlying cause of anaemia (e.g. iron, folate, treat underlying cause) * avoid bone marrow suppressing agents * consider EPO * optimise nutrition - * appropriate blood sampling (see above) Limit acute blood loss * find and stop bleeding early * correct coagulopathy (e.g. hemostatic resuscitation) autotransfusion and cell salvage

Answer 80

Transfusion target depends on multiple factors: Based on TRICC (1999) and NBA guidelines: Bleeding - aim Hb > 100 Non bleeding - aim Hb > 70 IHD and elderly - higher target ~ 100 Post cardiac surgical - Hb > 80 is non inferior to Hb > 90

Answer 81

Irradiated blood components are used to prevent Transfusion-associated graft-versus host disease (TA-GvHD) Indicated for: Immunocompromised patients, and specifically: Lymphoma Stem cell transplants Aplastic anaemia Immunocompetent patients receiving donated blood from relatives Anyone receiving granulocyte transfusions Anyone receiving HLA-matched platelets. Any neonates and any intrauterine transfusions

Answer 82

Transfusion reactions may be immune mediated or non immune. They may also be early < 24 hours or late > 24 hours Early < 24 hours: Allergy Acute Haemolytic reactions - ABO / Rh incompatability Bacterial contamination TACO TRALI Febrile - non immune reaction Post Transfusion TTP Late > 24 hours Non-immune haemolytic reactions Infection transmission - HIV / Hep B+C/malaria / CJD Bacterial infection Iron overload Microchimerism - the persistence of an allogeneic cell population of leucocytes transfusion mediated GVHD

Answer 83

Acute Haemolytic Transfusion reactions ( < 24 hours) * Interactions between antibodies in recipients plasma and antigens present on donor RBC * ABO and Rh D account for the majority of reactions * Most important naturally occurring Ab's - Anti A and Anti B - usually IgM subclass * ABO incompatibility ~ 1 in 50,000 transfusions * As little as 10 mls of incompatible blood can produce rapid reaction Investigations -> blood group and DAT on both pre and post transfusion samples, haemolysis screen, urinalysis

Answer 84

* Defined as hypoxia and bilateral pulmonary oedema occurring within 6 hours of transfusion in absence of alternative clear diagnosis * Incidence ~ 1 in 5000 plasma containing transfusions ( whole blood / FFP / PRBC) * Pathogenesis theory -> immune vs non immune ○ Immune -> presence of leukocyte antibodies in the donor plasma attach HLA antigens in recipient ○ Non-immune -> lipid mediated * Pathology: 2 hit model 1) Underlying illness primes e.g. critical illness initially makes patients more susceptible to acute lung injury 2) Transfusion leads to neutrophil activation -> complement activation -> endothelial cell damage and capillary leak (lungs) * DDx: Pulmonary oedema, TACO, neurogenic pulmonary oeeam, ARDS due to another causes. e.g. sepsis. Fat embolism * Rx: supportive * *Risk factor= e.g. FFP from multiparous women In contrast to ARDS - recover usually occurs within ~ 8 hours

Answer 85

* Post-transfusion purpura (PTP) is a rare delayed transfusion reaction where a patient develops dramatic, sudden and self-limiting thrombocytopenia (platelet counts <10 x 109/L in 80% of cases), typically 7 to 10 days after a blood transfusion. * RF: Females, young with either prior pregnancy or prior transfusion history * Ix: anti-platelet antibodies in patient plasma Rs: IvIg, steroids +/- PLEX

Answer 86

HUS AND TTP are very similar but renal involvement predominated in HUS Types: * Typical HUS (diarrhoea + infection) * Atypical HUS - rare- complement dysregulation, Typical HUS: (Diarrhoea) * >90% of cases * Preceding infection with a toxin producing bacteria - typically E.coli 0157:H7 Atypical HUS: (No diarrhoea) * Rare * Possibly familial, genetic predisposition * Pathophysiology -> complement dysregulation * Triggers: Streptococcus pneumoniae - > aka P-HUS - a subtype of Atypical HUS Pregnancy - usually at term or post partum Drugs -> QUININE, CICLOSPORIN Transplants - renal / HSCT HIV Classic Pentad (FAT R/N) * fever * anaemia (MAHA) * thrombocytopenia * renal problems (88% have renal problems, 15% haematuria) – more likely in HUS * neurological problems (headaches, confusion, seizures) – more likely in TTP Ix: MAHA Low platelets Low Hb - with polychromasia Shistocytes = 'helmet cells - fragmented parts of RBC seen in MAHA Positive Hamolysis screen Renal injury Renal biopsy - if safe to perform -> thrombotic microangiography, thrombi present If suspected atypical HUS -> genetic testing Management of HUS: * Supportive care is mainstay * Platelets are contraindicated - ongoing haemolysis * Plasmapheresis if not sure whether this is HUS or atypical HUS * PLEX avoided in Strep pneumoniae trigged P-HUS -anti-T IGM in the administered plasma may exacerbate disease * Evidence poor for steroids * Eculizumab for atypical HUS

Haematology and Oncology Flashcards

(110 cards)