Haem1 Flashcards

Question

QUESTION 38 Other than bacterial infections, opportunistic infection with which of the following is most likely to occur in a patient after induction chemotherapy for acute myeloid leukaemia (AML)? A. Candida albicans. B. Mycobacterium tuberculosis. C. Cytomegalovirus. D. Cryptosporidium. E. Toxoplasma gondii.

Answer 1

A. It is critical that the thrombocytosis and increased RBC mass is controlled pre-op otherwise the risk of arterial thrombosis is unacceptably high.

Answer 2

B. The EPO level is raised.

Answer 3

- JAK2 mutation - increased RBC mass - Splenomegaly - Normal arterial O2 - elevated WBC and platelets

Answer 4

Mechanism Acquired JAK2 exon mutation (95% of cases) —\> proliferation of all three haematopoietic cells lines (megakaryocytes, RBCs, myeloid) —\> prominent overproduction of RBCs and to a lesser extent, WBCs and platelets w/ low EPO level.

Answer 5

Clinical findings Expanded blood volume & viscosity —\> headache, dizziness, blurred vision, fatigue Histamine release from basophilia —\> fatigue Epistaxis and GI bleeds —\> abnormal platelet function and mucosal blood vessel engorgements Plethora, engorged retinal veins Splenomegaly Thrombosis is major cause of morbidity and death - due to viscosity and abnormal platelets. MUST control disease before any surgery

Answer 6

Epidemiology Men in their 60s, v rare under 40

Answer 7

Elevated HCT - \>54/51% M/F respectively Elevated RBC mass Elevated WBC and PLT counts Normal morphology of all three lines Basophilia and eosinophilia Low EPO levels JAK2 mutation positive BMBx - hyper cellular, panhyperplasia w/ absent iron stores (transferred to circulating RBCs) Very high B12 due to secretion of transcobalamin III from WBCs Hyperuricaemia Iron deficiency from bleeding & phlebotomy - microcytosis w/ normal HCT Elliptocytosis from progressive hypersplenism

Answer 8

Major Criteria (2 Mj + 1Mn or 1st Mj + 2Mn) Hb more than 185 in men, 165 g in women, or elevated red cell mass greater than 25% Presence of JAK2 617V greater than F or other similar mutations Minor Criteria BMBx: hypercellularity w/ prominent erythroid, granulocytic, and megakaryocytic proliferation. Serum erythropoietin level below normal range. Endogenous erythroid colony formation in vitro.

Answer 9

Spurious - elevated HCT due to volume contraction / diuretis Secondary - Hypoxia and smoking - carboxyhaemoglobin levels may be elevated - renal lesions (tumor, EPO secreting tumor (rare)) - Abnormal Hb (rare) - CML if very high WCC - Myelofibrosis if abnormal RBC morphology and nucleated RBCs - ET is ultra high PLT count

Answer 10

Phlebotomy to maintain HCT \<45%, need should gradually decrease as iron stores diminish, avoid supplementation. Decreases thrombotic complications Low iron diet increases intervals between phlebotomy If unable (high req, thrombocytosis, intractable pruritus) —\> hydroxurea 1st, anagrelide 2nd Reduction of platelet count reduces complications Avoid alkylating agents - increases risk of conversion to acute leukaemia All patients should receive aspirin, reduces thrombosis w/o risk of excessive bleeding Allopurinol for hyperuricaemia Antihistamines for itch, SSRIs if intractable

Answer 11

Indolent, median survival 11-15 years Arterial thrombosis major cause of morbidity and mortality May convert to myelofibrosis or CML 5% to AML (rare)

Answer 12

Pseudohyperkalemia is a rise in the amount of potassium that occurs due to excessive leakage of potassium from cells, during or after blood is drawn. Usually a lab artefact due to haemolysis during venepecture (excessive vacuum, too fine gauge), excessive tourniquet time, fist clench, delay in processing or tube dropping. Also can occur in _thrombocytosis_ (\>500), leukocytosis (\>70), or erythrocytosis (HCT \>55%)

Answer 13

Features - elevated platelet count - normal RBC mass - absence of BCR-ABL gene - uncommon

Answer 14

Mechanism Unknown cause (high freq of JAK2 mutation) —\> Proliferation of megakaryocytes —\> thrombocytosis —\> venous thrombosis

Answer 15

Epidemiology 50-60 year olds, slightly more in women, rare

Answer 16

Clinical findings Discovery of elevated platelet count Venous thromboses at unusual sights (i.e mesenteric, hepatic or portal vein Erythromelalgia (painful burning of the hands) Mucosal bleeding due to faulty platelets Splenomegaly in at least 25%

Answer 17

Elevated PLT over 1-2000 Mildly elevated WBC w/ immature myeloid forms Normal haematocrit Smear: Large platelets, but not giant or degranulated. Normal RBC morphology BMBx: Megakaryocytosis w/ no other morphologic abnormalities Cytogenetics: Absent BCR-ABL (need to do to rule out CML) JAK2 mutation in 50% of cases

Answer 18

Reactive thrombocytosis —\> PLT count not as high (less than 1000) Inflammatory disorders (RA, UC, chronic infection) Iron deficiency —\> but thrombocytosis only if significant anaemia Splenectomy → temporary thrombocytosis PCV - no erythryocytosis Myelofibrosis - normal RBC morphology, no nucleated RBCS, no giant degranulated platelets CML - BCR ABL negative.

Answer 19

Control platelet count w/ oral hydroxyurea, prevents thrombotic events w/o toxicity 2nd line anagrelide (low dose) - high dose = headache peripheral oedema and CHF Vasomotor sx (erythromelalgia and parasthesias) —\> aspirin Low dose aspirin may reduce risk of thrombotic complications Severe bleeding —\> plateletpheresis

Answer 20

Prognosis Indolent, high long term survival with control of thrombosis Late: fibrotic BM, massive splenomegaly and infarction 10-15% risk of progression to myelofibrosis, 1-5% risk of transformation to acute leukaemia

Answer 21

Features - striking splenomegaly - teardrop poikilocytosis - leukoerythroblastic bloods w/ giant abnormal plt - Hypercellular BM w/ reitculin or collagen fibrosis

Answer 22

Mechanism Increased secretion of platelet-derived growth factor —\> bone marrow fibrosis —\> extramedullary haematopoiesis (liver, spleen, LNs), reactivation of feral mesenchymal stem cells —\> splenomegaly, leukoerythroblastic blood film w/ teardrop poikilocytosis —\> anaemia, splenomegaly, BM failure

Answer 23

Epidemiology \>50, insidious

Answer 24

Fatigue due to anaemia Abdominal fullness and early satiety due to splenomegaly Massive splenomegaly Hepatomegaly in \>50% of cases Late: progressive thrombocytopaenia due to BM failure Painful episodes of splenic infarction Severe bone pain - esp upper legs Cachexia Portal HTN w/ ascites and varices due to hepatic haematopoeisis Occasionally: transverse myelitis due to epidural myelopoeises

Answer 25

Labs Anaemia Variable WCC (low/N/high) Smear: Significant poikilocytosis and teardrop RBCs, nucleated RBCs, left shifted myeloid series. Bizarre giant degranulated platelets Triad: teardrop poikilocytos, leukoerythroblastic blood, giant abnormal platelets BMBx: Dry tap usually but if early: hyper cellular with reticulin fibres on silver stain demonstrating fibrosis. Later: Collagen, no precursors JAK2 mutation in 65% of cases, MPL in 40%

Answer 26

Triad: teardrop poikilocytos, leukoerythroblastic blood, giant abnormal platelets

Answer 27

Leukoertyhroblastosis —\> severe infection, inflammation or infiltrated BM BUT no poikilocytosis/weird platelets BM fibrosis —\> metastatic ca, Hodgkin lymphoma, hairy cell leukaemia, need morphology CML —\> but normal RBCs w/ marked leucocytosis PCV - elevated haematocrit ET —\> platelet elevation dominant

Answer 28

**Tx** Mild —\> nothing Anaemia —\> transfusion +/- EPO Splenic enlargement / pain / severe thrombocytopaenia /high transfusion requirement —\> splenectomy Bone pain / Pulm htn —\> RTx Curative: Allo SCT Hydroxurea or lenalidomide may help control anaemia JAK2 inhibitors not on market yet

Answer 29

Prognosis Median survival - 5 years End stage—\> liver failure, bleeding from thrombocytopaenia, sometimes AML.

Answer 30

Iron deficiency Thalassemia Anemia of chronic disease Lead toxicity

Answer 31

Vitamin B12 deficiency Folate deficiency DNA synthesis inhibitors

Answer 32

Myelodysplasia Liver disease Reticulocytosis Hypothyroidism Bone marrow failure state (eg, aplastic anemia, marrow infiltrative disorder, etc.)

Answer 33

Kidney disease Mild form of most acquired etiologies of anemia

Answer 34

1. acute blood loss, 2. recent replacement of a missing erythropoietic nutrient 3. reduced red blood cell survival (ie, hemolysis)

Answer 35

A severely microcytic anemia (mean corpuscular volume [MCV \<70 fL) is due either to iron deficiency or thalassemia, while a severely macrocytic anemia (MCV \>125 fL) is almost always due to either megaloblastic anemia or to cold agglutinins in blood analyzed at room temperature.

Answer 36

- RBCs, ferritin and hemosiderin are major storage pools - 10% of dietary iron is absorbed - Absorbed in stomach, duodenum, jejunum under acidic conditions - 70% of iron is in RBCs - minor daily losses from sloughing of epithelial cells or insignificant blood losses - free iron can produce ROS —\> tissue damage, promotion of bacteria (who need it for growth

Answer 37

Iron transport - across intestinal lumen by ferroportin (it is exported from the basolateral surface of the enterocyte to the circulation) - ferroportin also facilitates transport of iron in macrophages and then to apotransferrin (transferrin) in RBCs for haemoglobin synthesis - Hepcidin (produced during iron loading and inflammation) promotes degradation of ferroportin by binding it —\> decreased release into circulation, sequestration of iron into macrophages, and decreased circulating iron - menstrual blood loss plays a major role in iron metabolism Anaemia of chronic disease —\> body iron stores not deficient but not available for RBC production due to hepcidin stimulation Hepcidin suppression: Fe deficiency, hypoxia, haemorrhagic or haemolytic anaemias —\> release of stored iron and increased dietary absorption In iron overload —\> hepcidin deficiency

Answer 38

Ferritin - intracellular storage protein - \<30 indicates iron deficiency - good marker of total body iron stores - low ferritin seen almost only in iron deficiency - do not reflect iron stores alone, normal-high levels does not exclude - elevated in inflammation, infection, malignancy (blood and solid), liver, kidney disease, high BMI, post-menopause - serum iron is poor measure, is a negative acute phase reactant in acute inflammation - level testing not currently available

Answer 39

Transferrin - carrier protein for iron - carries iron to transferrin receptor which endocytoses complex into cell which then releases iron for use or stores it - liver synthesis apotransferrin so high levels in Fe+ defiency or high oestrogen states, low levels may be due to liver disease or inflame, it is also a negative acute phase reactant

Answer 40

Soluble transferrin receptor - useful if presence of inflammation is obfuscating result (i.e. in inflammation) - upregulated when iron needs are increased (i.e. deficiency, or PCV) - not an acute phase reactant - testing not currently rebateable

Answer 41

Transferrin saturation - calculated ratio between serum iron and TIBC - hence influenced by anything that affects serum iron - elevation may be earliest indicator of hereditary haemochromatosis

Answer 42

Chronic blood loss (most important) - Esp GI - Aspirin/anti-inflams even w/o structural lesion - menorrhagia or uterine bleeding - repeated blood donations - chronic haemoglobinuria (uncommon): traumatic haemolysis (valve), or other intravascular haemolysis i.e. PNH. Menorrhagia and Pregnancy - iron deficient unless supplemented, diet alone doesn’t cut it Decreased absorption - coeliac disease, surgical stomach resection or jejunal bypass

Answer 43

Clinical findings Anaemia —\> fatigue, tachycardia, palpitations, SOBOE Severe: skin and mucosal changes, smooth tongue, brittle nails, spooning (koilonychia) and cheilosis (inflamed corners of mouth) Dysphagia due to oesophageal webs (Plummer-Vinson syndrome) in severe iron deficiency Pica: often for foods not rich in iron

Answer 44

Lab findings Initially iron deficiency w/o anaemia followed by anaemia and normal MCV, then hypo chromic microcytic anaemia Ferritin \<30 (or \<15 is v specific but not sensitive) Ferritin is an acute phase reactant so unreliable in response to inflammation - not ruled out if normal or elevated Transferrin elevates to compensate leading to transferrin saturations of less than \<15% (Serum iron : TIBC) however this ratio will be low in anaemia of inflammation too Anisocytosis (size) & poikilocytosis (shape) in more severe disease, followed by severe hypochromia, target cells, or pencil/cigar-shaped cells.

Answer 45

DDx Anaemia of chronic disease (normal or increased iron stores in BM macrophages, normal or elevated ferritin, serum iron and transferrin saturation is low, TIBC and transferrin n/low Thalassaemiea - greater degree of microcytosis for level of anaemia with normal or elevated RBC count (unlike every other cause of anaemia). Similar smear to severe iron deficiency

Answer 46

Treatment Identify cause Ferrous sulcate, go slower and lower for compliance Should be halfway toward normal within 3 weeks, full return to baseline after 2 months, continue for 3-6 months to replenish iron stores Failure mostly due to non compliance, sometimes poor absorption due to stomach achlohydria - give ascorbic acid Other: incorrect dx, ongoing GI blood loss Parenteral iron Indications: Intolerance to oral, refractory to oral, GI disease (usually inflammatory) New formulation is iron oxide coated in a carbohydrate Iron deficit = % iron deficit x normal RBC volume I.e. if the Hb is 75% of normal then it’s 0.25 x 27ml/kg (normal RBC volume) = 337.5 grams The dose is then iron deficit + 1 gram = 1.4gm

Answer 47

A. Inflammation. B. Pure red cell aplasia. – reticulocyte count normal C. Vitamin B12 deficiency. – not macrocytic D. Iron deficiency. – not microcytic, ferritin up so can’t say E. Hyperparathyroidism. – not significant

Answer 48

Essentials - mild-mod normocytic or microcytic anaemia - normal-increased ferritin - normal-reduced transferrin - underlying chronic disease

Answer 49

Mechanism - EPO resistance - inflammatory cytokines diminishing RBC production - in the elderly: decreased EPO production due to reduced nephron mass and low level chronic inflammation. Normal serum iron - low serum iron in inflammatory states

Answer 50

Lab findings - HCT rarely below 60% of baseline (except in renal failure) - normal or mildly reduced MCV - minimally changed reticulocyte count - low serum iron - low serum transferrin - normal to elevated serum ferreting (if \<30, coexistent iron deficiency) - in organ failure and elderly: normal iron studies - if ferritin super elevated —\> soluble transferrin receptor (high = iron deficiency - BMBx - absent iron staining, sequestration of iron in marrow macrophages but very rarely done. - ultimate test: Hb response to oral iron in setting of inflammation if iron deficiency is suspected.

Answer 51

EPO indicated in: - Hb \<10 & anaemia due to RA, IBD, Hep-C, Zidovudine in HIV, myelosuppresive chemo w/ solid malignancy and palliative intent, CKD with GFR \<60. - Aim for Hb 100-120, risk of VTE and ATE

Answer 52

A sign of ineffective erythropoiesis (expansion of the erythroid compartment of the bone marrow that does not result in the adequate production of reticulocytes in the peripheral blood).

Answer 53

Lead poisoning chelation

Answer 54

Diagnostic essentials - ringed sideroblasts in the BM - elevated serum Fe+ and transferrin saturation

Answer 55

**Mechanism** Reduced ability to synthesise or incorporate heme into protophyrin IX —\> accumulation of iron in RBC precursor mitochondria **Causes** - subtype of MDS most commonly - chronic alcholism - lead poisoning - drugs: isoniazid, chloramphenicol - chronic infection/inflamattion - inherited: x-linked

Answer 56

Clinical findings - anaemia Labs - sideroblastic MDS: Normal or slightly elevated MCV - all others: low - HCT of 20-30% (moderate anaemia) - elevated serum iron and transferrin saturation - smear: dimorphic RBCs (normal and hypo chromic), in lead poisoning: basophilic stippling, elevated serum lead - BMBx is diagnostic: marked erythroid hyperplasia with ringed sideroblasts (erythroid cells with iron deposits in mitochondria encircling nucleus) on Prussian blue iron stain.

Answer 57

Treatment - occasionally transfusions - do NOT respond to EPO therapy - occasionally pyridoxine - remove offending toxin/drug in secondary forms

Answer 58

BMBx is diagnostic: marked erythroid hyperplasia with ringed sideroblasts (erythroid cells with iron deposits in mitochondria encircling nucleus) on Prussian blue iron stain.

Answer 59

**Dietary deficiency (rare)** **Decreased production of intrinsic factor** - Pernicious anemia - Gastrectomy **Helicobacter pylori infection Competition for vitamin B12 in gut** - Blind loop syndrome - Fish tapeworm (rare) **Pancreatic insufficiency** **Decreased ileal absorption of vitamin B12** - Surgical resection - Crohn disease Transcobalamin II deficiency (rare)

Answer 60

- Macrocytic anemia. - Megaloblastic blood smear (macro-ovalocytes and hypersegmented neutrophils). - Low serum vitamin B12 level.

Answer 61

Physiology B12 a cofactor in conversion of homocysteine to methionine, and for conversion of methylmalonylcoenzyme A (CoA) to succinyl CoA —\> annulment of Okazaki fragments during DNA synthesis of erythroid progenitor cells Dietary B12 is animal in origin —\> —\> absorbed by ileum —\> liver stores 2-5mg while daily utilisation is 3-5mcg —\> takes 3 years for iron deficiency to occur

Answer 62

Clinical findings Slow onset mod-severe anaemia May be asymptomatic Later: leukopaenia and thrombocytoapaenia Mucosal disturbance —\> glossitis Anorexia and diarrhoea Neurology - peripheral nerves 1st —\> parasthesia —\> posterior column involvement —\> loss of balance or proprioception or both —\> later: dementia, neuropsychiatric abnormalities, decreased vibration and position sense Non-hematologic complications can occur w/ NORMAL FBC

Answer 63

Labs Low serum B12 (cobalamin \<170, symptomatic \<100 Best confirmed with an elevated level of serum methylmalonic acid (can also be elevated i kidney disease MCV \>110 (but can have normal MCV, esp with Fe deficiency or thalassaemia) Smear: Macro-ovalocytes (megaloblastic), hyper segmented neutrophils, reduced reticulocyte count, in severe cases: reduced WCC and PLTs (B12 deficiency affects all cell lines Elevated LDH and indirect bilirubin due to intramedullary destruction of abnormal RBCs, similar to peripheral haemolytic anaemias BMBx - erythroid hyperplasia, megaloblastic changes in erythroid precursors: abnormally large cell size, asynchronous maturation of the nucleus and cytoplasm (normal cytoplasm maturation, impaired DNA synthesis —\> abnormal nucleus)

Answer 64

DDx Other megaloblastic anaemias —\> but B12 will be normal MDS - different morphology, normal B12 and methylmalonic acid levels

Answer 65

Treatment IM daily for first week, weekly for first month, monthly for life Oral when corrected, even if pernicious anaemia as will be passively diffused if unable to be actively transported - continue indefinitely Concurrent folic acid required due to intestinal mucosal disruption for several months Hypokalemia may occur in first few days esp if anaemia severe Neurology reversible if \<6 months duration

Answer 66

Other megaloblastic anaemias —\> but B12 will be normal MDS - different morphology, normal B12 and methylmalonic acid levels

Answer 67

**Treatment** IM daily for first week, weekly for first month, monthly for life Oral when corrected, even if pernicious anaemia as will be passively diffused if unable to be actively transported - continue indefinitely Concurrent folic acid required due to intestinal mucosal disruption for several months Hypokalemia may occur in first few days esp if anaemia severe Neurology reversible if \<6 months duration

Answer 68

A. Results in B12 deficiency --\> megaloblastic anaemia

Answer 69

Dietary deficiency Decreased absorption - Tropical sprue - Drugs: phenytoin, sulfasalazine, trimethoprim-sulfamethoxazole Concurrent vitamin B12 deficiency Increased requirement - Chronic hemolytic anemia - Pregnancy - Exfoliative skin disease Excess loss: - hemodialysis Inhibition of reduction to active form - Methotrexate

Answer 70

- macrocytic anaemia - megaloblastic smear (macro-ovalocytes and hypersegmented neutrophils - normal serum B12 levels - reduced serum folic acid levels

Answer 71

Physiology - real name: pteroylmonoglutamic acid - citrus and leafy greens - stored for 2-3 months - absorbed throughout entire GI tract - absorption impaired by drugs or full length mucosal disruption - increased requirements in pregnancy, haemolytic anaemia and exfoliative skin disease

Answer 72

Signs and symptoms - anaemia - mucosal megaloblastic changes - NO neurological abnormalities

Answer 73

Macrocytic anemia. Megaloblastic blood smear (macro-ovalocytes and hypersegmented neutrophils). Normal serum vitamin B12 Low red blood cell folate (preferred as reflects stores over lifespan of RBC)

Answer 74

- B12 deficiency - check level - alcoholic nutritional deficiency —\> no megaloblastic changes but TARGET cells - hypothyroidism assoc w/ pernicious anaemia

Answer 75

Tx Daily PO folic acid, similar response as in B12 replacement - MUST check B12, large doses of folic acid will correct bloods but will allow ongoing neurologic damage.

Answer 76

B. Donor-recipient ABO blood group incompatibility.

Answer 77

E. veno-occlusive disease.

Answer 78

Mucositis (most common) Haemorrhagic cystitis Prolonged and severe pancytopaenia Infections CMV EBV Viral hepatitis Acute GVHD Graft failure Transplant related lung injury Hepatic veno-occlusive disease Transplant related MAHA

Answer 79

Mucositis - most common short-term complication - etoposide and MTx - can be oropharyngeal and intestinal - intubation if supraglottic - may need TPN - topical and systemic analgesia and opioids

Answer 80

Prolonged & severe pancytopaenia - common, lasts up to 4 weeks - empiric anti fungal tx if persistent unexplained fever in setting of use of broad-spectrum abc - antiviral prophylaxis usually given - serious infections (pneumonia, bacteraemia, fungaemia, viraemia) in up to 50% - more common in matched unrelated donors (MUDS) than auto or sibling allografts. - recombinant growth factors (filgrastim) started 24-72 hours post stem cell infusion reduce neutrophil recovery time - severe thrombocytopaenia —\> transfuse \<10, or 50 if surgery required. - severe anaemia —\> transfuse, sometimes EPO

Answer 81

Infections Early (0-30 days) - mucosal and skin injury —\> aerobic bacteria (esp coag -ve staph, viridans step, gram -ve’s candida and HSV). Mid 1-3 months: T-cell dysfunction, hypogammaglobulinaemia —\> encapsulated bacteria (pneumococcus, H.influenzae), viruses (CMV, PHP), molds and candida Later 3-12 months - t-cell reconstitution, chronic GVHD —\> encapsulated bacteria, CMV, PJP, HZV, EBV and hepatitis

Answer 82

CMV - due to impaired viral immunity in first year, acute or chronic GVHD - CMV positivity = higher peritransplanatation mortality rate. - treated prophylactically and preemptively to prevent pneumonitis and viraemia but can still occur EBV - most common in patients who are EBV naive, in patients receiving T-cell depleted grafts, or receiving ATG for in-vivo t-cell depletion. - causes posttrantplant lymphoproliferative disorder (PTLD) in HSCT, t-cell depleted grafts, and those undergoing intensive tx for GVHD

Answer 83

Viral hepatitis - third most common cause of liver disease in transplant patients - can reactivate HBV at 3-6 months due to impaired cellular immunity - HBsAg +ve = prophylactic antiviral tx pre-chemotherapy and for 3/12 after. - if -ve, need vaccination before transplant - HCV has little impact but is a risk factor for hepatic veno-occlusive disease and GVHD - faster progress of HCV to fibrosis and cirrhosis, decompensation and malignancy in HSCT. Third leading cause of late deaths after transplant - need definitive management after 6 months and no evidence of GVHD.

Answer 84

Donor immunocompetent T-cells and NK cells recognise host antigen as foreign —\> immune reaction - mainly in allograft setting (not auto or syngeneic (twin) - severity of GVHD inversely related to risk of relapse due to relationship with graft-versus-leukaemia effect. - reduction achieved by optimising donor and graft type and post-transplant immunosuppresion. - least with peripheral blood HSCT, worst with umbilical cord HSCT

Answer 85

- common, within first 100 days - skin, mucosa, gut, and liver - erythematous macular skin rash —\> blistering (like burns), severe abdominal pain, profound diarrhoea, hyperbilirubinaemia. - Stage 1 skin up to stage IV (systemic). III-IV have a bad prognosis. - RFs: HLA mismatch, MUD grafts, grafts from a parous female donor, older age - pathogenesis: acute cytokine storm (TNF and IL-1) released due to damaged host tissue from induction —\> increased MHC expression —\> recognition of minor HLA differences by T-cells —\> proliferation and cytokine release —\> further recruitment of t-cells and macrophages —\> release of TNF and IL-1 —\> vicious cycle of inflammation and tissue damage - prophylaxis better than treatment: graft t-cell depletion (but increased risk of graft failure and rate of relapse due to graft vs tumour effect - prevention: CNi (renal toxicity) + MTx (but mucositis), sirolimus and MMF have less toxicity. Can also use gut decontamination with metro, IVIG or less intensive regiment - high dose steroids and ATG does not work.

Answer 86

- 40-80% of long term survivors, incidence rising as older patients get transplants - RFs: peripheral blood transplants, mismatch or unrelated donors, second transplant, donor leukocyte infusions - greatest risk for chronic GVHD is acute GVHD - 2-12 months post transplant - skin, eyes, mouth, liver, fascia, any organ - chronic lichenoid skin changes, dry eyes and mouth, impaired ROM from fibrosis of dermis and fascia. Resembles scleroderma or other autoimmune diseases - immunosuppression with steroids, tacrolimus and MMF are mainstays, hydroxychloroquine works well too. - major cause of death: profound immunodeficiency, need prophylaxis against encapsulated organisms - patients with frequent infections and low Ig levels should get IVIG

Answer 87

Graft failure - associated with HLA mismatch, more frequent in MUD grads - other RFs: aplastic anaemia, t-cell depletion, infusion of lower number of stem cells (cord blood), nonmyeloablative transplants, GVHD, splenomegaly - poor graft function can be treated with growth factors (G-CSF or GM-CSF), and EPO. - Failure: second stem cell infusion

Answer 88

Transplantation-relation lung injury (TRLI) - acute inflame response —\> severe lung injury - allogenic transplant - early tx w/ corticosteroids and etanercept (anti-TNF) reduces extent Interstitial pneumonitis (usually CMV) is frequently fatal - reduced w/ anti-infective prophylaxis and CMV-ve blood products (leukodepletion, CMV -ve donors), tx w/ ganciclovir or foscarnet + IvIg Autograft - diffuse alveolar haemorrhage RTx or pulm toxins, MTx or carmustine

Answer 89

Hepatic veno-occlusive disease (Sinusoidal Obstruction Syndrome) - very common, potentially lethal - 10-60% of patients, 50% of post-transplant deaths - weight gain, tender hepatomegaly, jaundice and ascites —\> fulminant multiorgani failure - 8-10 days post inductions - RFs: prior liver damage, high levels of busulphan, \>10-12 Gy total body irradiation, heavy induction, C282Y positivity of haemochromatosis gene - pathology: elevated TNF —\> sinusoidal endothelial damage —\> sloughs —\> obstructs hepatic circulation —\> centrilobular hepatic injury and portal hypertension. - Prevention is best treatment: avoid fludarabine or cyclophosphamide, use nonmyeloablative regiment - Ursofalk reduces risk of this and grades III-IV GVHD - Treatment is supportive, with defibrotide which is antithrombotic and fibrinolytic (avoid heparin and TpA)

Answer 90

- organ toxicity from chemo - posttransplanation immunosuppression - Chronic GVHD - endocrine disease and heart failure - increased risk of malignancy years later: acute leukaemia’s, solid tumours, MDS, disease and regimen dependent, increased prevalence after total-body irradiation - late infections (months), usually in assoc w/ GVHD or GVHD therapy - Vaccines: pneumococcus, H.influenzae, Hep-B, polio, ADT, influenza - recommence at 18 months Ocular - cataract formation - dry eyes due to chronic GVHD Bronchiolitis obliterans - HSCT recipients, fatality rate 50% - no response to steroids MSK - OP, and avascular necrosis - bisphosphonates Neuropsych disorders - usually due to cranial irradiation

Answer 91

- host immunity suppressed months-years - worse after allograft - related to severity of induction, acute GVHD, ongoing immunosuppression for GVHD - complete reconstitution may take years due to less active (or even absent) thymic function the older you get.

Answer 92

Donor must be matched with the patient (recipient) at the HLA loci (HLA A, B, C, DR) that specify major histocompatibility antigens.

Answer 93

- umbilical cord blood units may also be used. - bone marrow - more commonly through leukopheresis of the blood after mobilizing hematopoietic stem cells from the bone marrow with filgrastim (G-CSF).

Answer 94

There is a period of pancytopenia in the gap between the effect of the chemotherapy given to the patient and the time it takes the infused hematopoietic stem cells to grow into bone marrow, usually 10–14 days.

Answer 95

GVH is the major cause of morbidity and mortality during an allogeneic SCT. Immunosuppression must be given during allogeneic stem cell transplantation to reduce the incidence and severity of GVH reaction. CnI plus MTx

Answer 96

In most cases of allogeneic stem cell transplantation, the immunosuppression can be tapered and discontinued 6 or more months after transplantation.

Answer 97

Residual cancer cells can be recognized as foreign by the donor immune system and killed. Intensity of GVHD correlates with GVM (rate of graft failure is inversely proportional to severity of GVHD) Reducing the intensity of the induction regimen, relying for cure more on the GVM effect than the myeloablation. Allo-SCT is now being offered up to age 60 in some cases.

Answer 98

Acute leukaemias (AML, ALL) MDS CML (refractory to TKIs) Severe aplastic anaemia

Answer 99

Bone marrow failure Autograft - G-CSF is given --\> stem cells are collected from peripheral blood pre treatment --\> induction Ctx (to kill cancer) --\> reinfused post

Answer 100

7-10 days Transfusion and antibiotics

Answer 101

DLBCL recurrence after chemo but still responsive to chemo Responsive relapsed Hodgkin's lymphoma Recurred testicular germ cell tumours

Answer 102

Autologous stem cell transplantation is currently part of the standard of care for the treatment of mantle cell lymphoma and multiple myeloma, based not on curative potential, but the prolongation of remission and overall survival.

Answer 103

Acanthocytes arise from either of two mechanisms. Alterations in membrane lipids are seen in abetalipoproteinemia and liver dysfunction. Alteration in membrane structural proteins are seen in neuroacanthocytosis and McLeod syndrome. In liver dysfunction, apolipoprotein A-II deficient lipoprotein accumulates in plasma causing increased cholesterol in RBCs. This causes abnormalities of membrane of RBC causing remodeling in spleen and formation of acanthocytes.

Answer 104

 Leucodepletion is the removal of white blood cells from a blood component. Applies to whole blood, red cells and platelets. Benefits: - Reduction in platelet refractoriness  - Reduction in febrile non-haemolytic transfusion reactions. (FNHTR)  - Reduction in CMV transmission risk  - Improved chance of finding an organ transplant match if required  - Reduction in storage lesion effect  - Possible reduction in transfusion associated graft vs host disease (TA-GVHD) risk

Answer 105

O, A, and B negative blood only (Negative can only receive negative, never positive)

Answer 106

A, B and O all positive or negative Positive blood groups can receive negative matches.

Answer 107

A-, A+ or O +/- (Positive can receive negative or positive) (O bloods do not have A or B antigens)

Answer 108

A- or O- only Negative can only receive negative O does not have A or B antigens but still carries rhesus status.

Answer 109

B +/-, O+/- Positive can receive positive or negative O does not carry A or B antigens, only rhesus status

Answer 110

B- or O- blood. Negative can only receive negative O has no A or B antigens, only rhesus.

Answer 111

O- can only receive O- O+ can receive both O+ and O- No A or B can be given because the recipient will have antibodies Negative can only receive negative O does not have A or B antigens

Answer 112

Rare blood types Occasionally - severe leukoagglutinin reactions or anaphylactic reactions

Answer 113

If you lack one, you have an IgM isoantibody to it (isoagglutinin) --\> complement gets activated --\> rapid intravascular lysis.

Answer 114

It does not have A or B antigens, and thus can be given to anyone. PRBCs can only be given (the plasma has to be separated out) because the donor plasma contains Anti-A or Anti-B antibodies.

Answer 115

Rh D antigen is highly immunogenic Anyone who receives D+ blood when they are D- will subseuqnetly make highly active anti-D antibodies that cause severe lysis of subsequent transfusions of D+ red cells or to a future rhesus positive baby

Answer 116

Stops allo-immunisation by destroying any Rh-D positive fetal erythrocytes that get through to the maternal system before the mother can make her own antibodies. Prevents haemolytic disease (rhesus disease) of the newborn. Okay if you have an RH+ mother and an Rh- fetus

Answer 117

Acute ABO incompatibility - isoagglutinin mediated Mostly due to clerical errors and mislabelled specimens Rapid intravascular haemolysis - most severe usually when the patient is under anaesthesia Delayed Minor RBC antigen discrepancies, less severe, IgG alloantibody mediates 5-10 days post transfusion Most common antigens are duffy, Kidd, Kell and Rh C and E SSx Fever, chills, backache and headache Apprehension, dyspnoea and hypotension Generalised bleeding and oliguria Severe: DIC, ARF due to ATN Delayed: usually w/o SSx Tx - hydration, maybe forced diuresis with mannitol

Answer 118

Leucocyte rich blood products esp platelets cause - happens in 1-2% of transfusion Fevers and chills within 12 hours post No haemolysis Responds to panadol and dipenhydramine, steroids Less of an issue now with leuco depletion Different to a hypersensitivity reaction

Answer 119

Exposure to allogeneic plasma proteins (not leukocytes) Anaphylactic shock may develop in IgA deficient patients because of IgA antibodies in the plasma component of the donor product. May require washed or frozen PRBCs next time.

Answer 120

Platelets especially because they cannot be refrigerated Gram positive contaimination will cause fever and bacteraemia but rarely sepsis. Gram negative will cause septic shock, acute DIC and ARF due to transfused endotoxin - usually fatal. Reduced by Aseptic technique Diverting first few ml of donated blood Single donor products (instead of pooled) POC bacterial screening to discard dodgy units

Answer 121

All blood products can. Risk of post-transfusion viral hepatitis is very low. Leukodepletion has greatly reduced CMB transmission, possibly equivalent to CMV-screened negative blood products.

Answer 122

Usually fatal, fever, rash, diarrhea, hepatitis, lymphadenopathy and severe pancytopaenia Usually in patients with immune defects, malignant lymphoproliferative disorders, chemo or immunotherapy, immunosuppression, old patients getting cardiac surgery HIV alone does not increase risk Leukodepletion doesn't avoid, need to irradiate the blood products if high risk.

Answer 123

Transfusion-related Acute Lung Injury Allogeneic antibodies in donor plasma bind to recipient leukococyte antigens including HLA, granulocyte and monocyte specific. Definition: Non-cardiogenic pulmonary oedema after a blood product transfusion without other explanation. Surgical and critically ill patients most susceptible. Reduced with male only plasma, treated with supportive care.

Answer 124

\<80 \<5 Given when less then 10 In thrombocytopaenia pre-op patients, goal is to get the platelet count \>50

Answer 125

Fever, sepsis Splenomegaly Lagre habitus Low platelet dose in transfusion Platelet alloimmunisation from prior transfusion Prior pregnancy Prior organ transplantation May get alloantibodies directed at HLA antigens - can get HLA matched antigens if this is the case.

Answer 126

Must be ABO matched Must be irradiated to prevent lymphocyte proliferation and prevent GVHD without funcitonal harm to the granulocytes or containing platelets. BUT not commonly used anyway

Answer 127

Recipient has antibodies to donor antigens on leukocytes (granulocytes) due to previous transfusion or pregnancy. Leucodepletion reduces febrile non-haemolytic transfusion reactions as a result.

Answer 128

Antiplatelet antibody to glycoprotein IIb/IIa or Ib/IX on the platelet membrane --\> platelet destruction --\> mucocutaneous bleeding

Answer 129

Primary / idiopathic Medication related (Thiazides, penicillin, GPIIB/IIIa inhibitors (ie tirofiban, Heparin) Hep-C HIV

Answer 130

HIV: Direct suppression of platelet production Hep-C: Cirrhosis related splenomegaly

Answer 131

Mucocutaneous bleeding: nosebleeds, gingiva Spontaneous bruising Usually at PLT counts \<20-30 Disease specific findings if HIV or Hep-C

Answer 132

Isolated thrombocytopaenia Anaemia if they've bled Exclude HIV and Hep-C BMBx for cytopaenias if over 60 or failed to respond to ITP therapy Megakaryocyte abnormalities are not ITP

Answer 133

Treat when PLT \<20-30 or significant bleeding Mainstay: short course of corticosteroids however most relapse. Plus or minus IVIG or anti-D (WinRho) Persistent plt count \<30 after roids: second line treatment (anti D, IviG are both temporary), rituxmiab works in up to 50%. Splenectomy an option

Answer 134

Eltrombopag Romiplostin Used in chronic ITP for people who have not responded to corticosteroids, IvIG or splenectomy or in cirrhosis due to hep-C. Must be taken indefintely

Answer 135

Patients should receive pneumococcal, Haemophilus influenzae type b, and meningococcal vaccination at least 2 weeks before the procedure

Answer 136

The goal of management of pregnancy-associated ITP is a platelet count of 10,000–30,000/mcL in the first trimester, \>30,000/mcL during the second or third trimester, and \>50,000/mcL prior to cesarean section or vaginal delivery. Moderate-dose oral prednisone or intermittent infusions of IVIG are standard.

Answer 137

Treatment of either infection improves platelet count in most cases Refractory thrombocytopenia may be treated with infusion of IVIG or anti-D (HIV and hepatitis C virus), splenectomy (HIV), or interferon-alpha or eltrombopag (hepatitis C virus, including eradication). Treatment with corticosteroids is not recommended in hepatitis C virus infection.

Answer 138

E. Platelet count gets treated when \<30 in refractory cases or if bleeding.

Answer 139

Idiopathic and autoimmune (mediated by T-lymphocytes or IgG antibody to erythroid precursors. Viral: (parvo, herpes, HIV and hepatitis) Thymoma Other malignancy Drugs: EPO (alpha aka Eprex), MMF Severe and normochromic with absent retics BMBx: All non- erythroid elements are present and normal, but erythroid precursors are markedly reduced or absent. In some cases, chest imaging studies will reveal a thymoma. Combination of antithymocyte globulin and a calcineurin inhibitor (cyclosporine or tacrolimus)—similar to therapy of aplastic anemia.

Answer 140

Neutralising antibodies, and will cross-react with all currently available erythropoietic agents (epoetin alfa and beta, and darbepoetin alfa), in addition to endogenous EPO.

Answer 141

Spherocytes are found in hereditary spherocytosis and autoimmune hemolytic anemia.

Answer 142

Ring sideroblasts are named so because of the arrangement of the iron granules in a ring form in mitochondria around the nucleus of an erythroid precursor The body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently.

Answer 143

- cytopaenia with hyper cellular BM (but not more than 20% blasts otherwise it's AML) - morphologic abnormalities in two or more cell lines

Answer 144

Idiopathic / cytotoxic CTx, RTx or both Benzene Red cell aplasia and Fanconi's anaemia can transform to MDS

Answer 145

Refractory anaemia - no excess bone marrow blasts, may or may not have ringed sideroblasts Refractory anaemia w/ excess blasts Chronic myelomonocytic leukaemia - MDS + peripheral blood monocytosis Prognosis worsens with each.

Answer 146

Myelodysplasia with: 5q- syndrome (indolent disease) Refractory anaemia with loss of long arm of chromosome 5 Good prognosis

Answer 147

IPSS - survival and rate of progression AML Survival related to: Percentage of bone marrow blasts 0-10% mild, 21-30% is poor Karyotype: Normal, Y-, 5q-, 20q- = good Bad: Cr 7 (monosomy 7), or if there are 3 or more abnormalities Cytopaenias - None or 1 cell line is good, 2 or 3 is bad.

Answer 148

Clinical findings Age \>60 Incidental finding or fatigue/infection/bleeding due to bone marrow failure Fever, weight loss, general debility Splenomegaly, pallor and bleeding

Answer 149

Marked anaemia w/ normal or elevated MCV Low WCC and neutropenia Smear: Macro-ovalocytes, bilobed neutrophils (Pelger Huet abnormality), myeloid left shift with small numbers promyelocaytes or blasts, normal or reduced hypo granular platelets BMBx: Erythroid hyperplasia, megaloblastosis: nuclear budding, multinucleate erythroid precursors Left shifted myeloid series, characteristic: dwarf megakaryocytic with a unloved nucleus Prussian blue stain: ringed sideroblasts

Answer 150

AML: MDS has \<20% blasts, AML has \>20%

Answer 151

EPO if anaemic if EPO levels are low G-CSF may help response to EPO. Highest transfusion requirements = least likely to respond Lenalidomide for transfusion dependent anaemia due to MDS esp for 5q- syndrome (less success w/o it). SEs: neutropenia, thrombocytopaenia, VTE - must use aspirin prophylaxis. Not useful for other cell lines. Iron chelation if transfusion dependent. High risk - azacitidine

Answer 152

Ultimately fatal, cure rates of 30-60% 5q- 5 year survival over 90% or low risk disease Excess blasts or CMML = higher chance of AML and short survival w/o Allo SCT.

Answer 153

Pancytopenia. Splenomegaly, often massive. Hairy cells present on blood smear and especially in bone marrow biopsy

Answer 154

Rare mature b-lymphocytosis with hairy cytoplasmic projections.

Answer 155

Middle aged men, 55 years 5:1 M:F Fatigue Sx related to markedly enlarged spleen Recurrent infection inc mycobacterial infections Hepatomegaly in 50% No lymphadenopathy

Answer 156

Pancytopaenia (hallmark) Anaemia (universal), thombocytopaenia and neutropenia Smear: ‘hairy cells’ B-lymphocytes with cytoplasmic projections BMBx: dry tap Splenic infiltrate of red pulp with hair cells (lymphoma it’s the white pulp) Immunophenotyping: CD11c, CD20, Cd22, CD25, CD103, and CD123

Answer 157

IFN-a Cladribine (purine analogue) Pentostatin

Answer 158

Good - \>95% of patients are alive longer than 10 years If secondary to CLL - worse prog

Answer 159

Monoclonal IgM paraprotein BM infiltration by plasmacytic lymphocytes Absence of lytic bone disease

Answer 160

IgM hypergammaglobulinaemia in setting of NHL. B-lymphocytes that are a morphological hybrid of lymphocytes and plasma cells. Cells secrete IgM paraprotein.

Answer 161

Insidious onset in 60s-70s Fatigue related to anaemia Hyperviscosity --\> mucosal and GI bleeding, retinal vein engorgement due to engorged blood vessels and platelet dysfunction --\> neuro sx, nausea, vertigo, visual changes, stupor, coma --\> cold agglutinin disease (haemolysis), chronic demyelinating peripheral neuropathy Hepatosplenomegaly Purpura No bone tenderness No renal disease No lytic lesions

Answer 162

Anaemia, roleaux, RBC agglutination at rom temp Anaemia is secondary to expansion of plasma volume (by 50-100% Plasmacytic lymphocytes on smear BMBx: Infiltration of plasmacytic lymphocytes Hallmark: Monoclonal IgM spike on serum PeP in the B-globulin region High serum viscosity (symptoms develop at 4x water viscosity, severe at 6x Positive Coombs for complement Cold agglutinin or cryoglobulin properties

Answer 163

Temp must be maintained at body temp of 37c or the paraprotein may precipitate out. Sample should recollected and kept warm.

Answer 164

MGUS --\> W has monoclonal malignant cells CLL --\> Absence of CD5, different morphology, absence of lymphocytosis Multiple myeloma --\> BM morphology, IgM paraprotein, absence of bone and renal disease

Answer 165

Hyperviscosity syndrome (stupor, coma, pulm oedema) --\> emergency --\> plasmapheresis Otherwise Periodic plasmapheresis FCR (Fludarabine, cyclophosphamide, rituximab)

Answer 166

Rituximab (anti-CD20 antibody)

Answer 167

Median survival of 5 years, 10% alive at 15 years.

Answer 168

C. This is hyperviscosity syndrome in Waldenstrom's macroglobulinaemia.

Answer 169

Congo red positive amyloid protein on tissue biopsy Amyloid protein is kappa or lambda Ig light chain Serum or urine (or both) positive for light chain paraprotein

Answer 170

Disturbed translational or post-translational protein folding --\> input of protein into tissues exceeds output --\> abnormal tissue deposition --\> organ dysfunction and failure

Answer 171

1. **Primary.** Ig light chain (AL Amyloidosis) 2. **Secondary.** Serum protein A, produced in inflammatory conditions (AA amyloidosis) 3. **Hereditary** (Transthyretin (TTR), senile amyloid (ANP) + tohers 4. **Renal Failure type** (B2 microglobulin not filtered out by dialysis membranes) AB₂M amyloidosis

Answer 172

Localised: SSx related to organ i.e. hoarseness, proptosis Systemic: Cardiac failure (infiltratrive/restrictive cardiomyopathy) Nephrotic syndrome Malabsorption and weight loss Autonomic insufficiency Carpal tunnel syndrome (bilateral) Sensorimotor peripheral neuropathy Enlarged tongue, waxy plaques on skin, periorbital contusions, cough or dyspnoea, decreased swallowing Insidious onset, dx made late in disease

Answer 173

Dx requires tissue biopsy that stains pink on H&E, _red on Congo red_, that becomes apple-green when the light is polarised. Kappa or _lambda (lambda more common) light chains_ in serum urine on PEP, IFE or free light chain assay in 90%, mass spectroscopy will catch the rest on tissue bx Systemic: Blind aspiration of _abdominal fat pad_ will reveal amyloid 66% of the time. Ventricular wall thickening on TTE with unique speckling pattern, low QRS voltages Renal: nephrotic range albuminuria; late: renal failure

Answer 174

MGUS, MM, or other malignant lymphoproliferative diseases. 12% of MGUS patients will convert to AL amylodoisis 1/5 of patients will meet crtieria for MM 5% of MM patients will have amyloid deposition of their paraprotein

Answer 175

Reduce light chains to protect organs - melphalan and pred - ASCT but not generally tolerated, and can't be done if advanced cardiac amyloidosis Thalidomide being tested

Answer 176

Prognostic indicators: BNP, tropT and tropI regardless of overt cardiac involvement Poor survival, even with ASCT, median sruvival approaches 5 years Monitored with serum free light chains.

Answer 177

Triple-stranded fibril that forms beta pleated sheets. Composed of amyloid protein P, and glycosaminoglycan.

Answer 178

Serum amyloid A protein (SAA) is an acute-phase reactant that is deposited in the tissues in AA amyloidosis. Involved in cholesterol transport.

Answer 179

Basic component of amyloid regardless of amyloid disease type.

Answer 180

Thrombocytopaenia within 5-10 days of espoxure to heparin Drop in baseline PLT count of 50% or more Thrombosis in 50% of cases, bleeding is uncommon

Answer 181

Heparin \> LMWH --\> formation of antibodies to heparin-platelet factor 4 complexes --\> antibodies bind platelets --\> activates them --\> thrombocytopaenia, pro-thrombotic state

Answer 182

Asymptomatic Thrombosis (venous or arterial) may be detected in up 50% of patients up to 30 days post dx

Answer 183

New onset thrombocytopaenia within 5-10 days of exposure to heparin (rapid onset HIT is not common) Drop of PLT count to 50% or more of baseline Positive 4T score Dx confirmed through positive PF4-heparin antibody enzyme-linked immunosorbent assay (ELISA) or functional assay (serotonin release assay) or both Magnitute of positive ELISA result correlates with clinical probability of HIT.

Answer 184

Measure serotonin release - a marker of platelet activation If release is high, the test is positive and the platelets are activated. Used in HIT.

Answer 185

STOP all forms of heparin. Doppler lower limbs Start alternative anticoagulant --\> usually a direct thrombin inhibitor (argatroban or lepirudin). Continue until PLT 100 then start Warfarin. If using argatroban, cease infusion prior to measuring INR 2 hours early so you know the anticoagulant effect is from Warfarin alone Warfarin contraindicated initially as may transiently worsen hypercoagulability. Continue Warfarin for 30 days due to persisten risk of thrombosis even if normal platelet count. If HITS plus thrombosis, Warfarin for 3-6 months Avoid subsequent exposure to Heparin, if absolutely necessary, measure PF4-antibdoies which should be negative (at about 100 days) and limit exposure to heparin.

Answer 186

Sign found in certain cancers that is associated with venous thrombosis and hypercoagulability. It is characterized by successive crops of tender nodules in affected veins.

Answer 187

1. Thrombocytopaenia - 2 points if the count falls \>50%, no points if it's less than \<30% 2. Timing of platelet count fall. 2 points if 5-10 days or if PLT count falls \<1 day with heparin exposure within 30 days. 3. Thrombosis. 2 points if new thrombosis, skin necrosis, or acute systemic reaction to unfractionated heparin bolus. 4. Other causes of Thrombocytopaenia. 2 points if none. Zero points if you can find another cause. Very good at excluding cases of HITs (NPV of almost 1). Low probability means you can exclude, intermediate and high require further investigation.

Answer 188

Fibrin degradation product present in blood after a clot is degraded by fibrinolysis - contains two crosslinked fragments of fibrin protein

Answer 189

Prolonged APTT and PT Decreased fibrinogen Thrombocytopaenia

Answer 190

Uncontrolled local or systemic activation of coagulation —\> depletion of coagulation factors and fibrinogen, activation and consumption of platelets leading to thrombocytopenia

Answer 191

Sepsis - coagulation activated by LPS Cancer Trauma Burns Pregnancy associated (tissue factor) Aortic aneurysm & cavernous haemangiomas Snakebited due to exogenous toxins

Answer 192

BLEEDING esp at IVCs or incisions May be widespread (purport fulminates) Malignancy related - thrombosis (trousseau syndrome)

Answer 193

Acute and progressive prolongation of coats and thrombocytopenia Early: PLT and fibrinogen may remain normal Progressive thrombocytopenia Elevated d-dimer due to activation of coagulation and diffuse cross-linking of fibrin Schistocytes on blood smear due to shearing through microvasculature HELLP of pregnancy: haemolysis, deranged LFTs, thrombocytopenia, renal dysfunction with gross haemoglobinuria and pigment nephropathy Malignancy-related: normal PLT counts and coags

Answer 194

Treat underlying cause Monitor PT aPTT fibrinogen and PLT count 6 hourly Give PLTs and aim count \>20, or \>50 if bleeding Cryo to replace fibrinogen (\>8-10) FFP to get PT and aPTT down PRBCs to get Hb \>80 Heparin if persistent bleeding to stop thrombin generation and thus consumption of coal proteins and platelets. Contraindicated if PLT \<50, bleeding, placental abruption or any need for surgery HELLP —\> evacuate uterus (deliver baby, remove retained placenta or fetal fragments) Trousseau syndrome —\> treat malignancy and give heparin to treat thrombosis (Warfarin doesn’t work) APL associated DIC —\> immediate (within 24h) chemotherapy plus blood products as required.

Answer 195

HELLP of pregnancy: haemolysis, deranged LFTs, thrombocytopenia, renal dysfunction with gross haemoglobinuria and pigment nephropathy leads to DIC Evacuate the uterus.

Answer 196

Elderly Malignancy CTD Postpartum or postsurgical

Answer 197

Soft-tissue ecchymoses, haematomas, mucosal bleeding (as opposed to haemoarthrosis in congenital haemophilia A)

Answer 198

- prolonged APTT that does not correct on mixing - low factor VIII activity - Bethesda assay will give you titre Treatment Low titre - give high doses of factor VIII High titre - prothromboninex or recombinant activated factor VII - plus steroids or cyclophosphamide Refractory: IVIG, ritux or plasmapheresis

Answer 199

Measure of the variation of red blood cell (RBC) volume that is reported as part of a standard complete blood count. Usually red blood cells are a standard size of about 6-8 μm in diameter. Certain disorders, however, cause a significant variation in cell size. Higher RDW values indicate greater variation in size.

Answer 200

Four criteria, need 3/4 for definite, 2/4 for posible. 1. Spontaneous recurrent epistaxis 2. Multiple telangiectasias in typical locations 3. Proven visceral AVM (lung, liver, brain, spine) 4. First-degree family member with HHT

Answer 201

Spontaneous, recurrent epistaxis - 90% Skin telangiectases - 75% Hepatic or pulmonary involvement (arteriovenous malformations [AVMs]) - 30% Gastrointestinal (GI) bleeding - 15%[31] CNS lesions inc headache

Answer 202

Expressed on activated platelets helps platelets adhere to damaged endothelium and to stick to one another

Answer 203

but no clinical change on bleeding time

Answer 204

but it has not normalised. Need to get within 4-5 seconds of the control (in this example up to 28s) to have 'normalised'; 32 shows there's still some inhibitor at work

Answer 205

ie Factor 7!

Answer 206

1-5% - minor trauma gives bleed

Answer 207

ie haemophilia mutation came on spontaneously

Answer 208

good for dental procedures - use as mouthwasy or oral tablets

Answer 209

the stronger) inhibitors against (recombinant) factor

Answer 210

all pts with mild Type 1 vWD and pts with mild haemophilia A should receive what treatment as first-line therapy (prophylaxis/treatment) of low risk ops / slight bleeds? DDAVP

Answer 211

antibodies bind to platelet factor 4 (PF4)

Answer 212

eg lepirudin or argatroban or fondaparinux) and start warfarin for 3 months (as HITs is a procoagulant state)

Answer 213

and restart when INR lower

Answer 214

dental work)? Keep on with the warfarin

Answer 215

anti-B and anti-Rh D antibodies. Checks for antigens on pt's RCs. Agglutination = positive.

Answer 216

why do we do leucodepletion? Why do we do irradiation? Leucodepletion - to reduce febrile non-haemolytic transfusion reaction due to HLA sensitisation or release. "CMV safe".

Answer 217

it's a prothrombotic agent

Answer 218

who has had prior clots but no pregnancy complications? Therapeutic anticoagulation

Answer 219

can't HDx off

Answer 220

but not thrombin that is bound to clots False; inhibits both free & clot-bound thrombin

Answer 221

80% renally excreted

Answer 222

apixiban too)

Answer 223

which is vast majority of cases)

Answer 224

hyperthyroidism

Answer 225

like 'me too!'. 3 is not good at being absorbed and our body actively changes Fe3+ to Fe2+ (via duodenal cytochrome B).

Answer 226

Fe3? Ferric Fe3 - ric is ick! We don't like it

Answer 227

we like this best

Answer 228

and reticulocytes should increase after 1-2 weeks (in response to making mor eiron)

Answer 229

increases iron absorbtion

Answer 230

liberation depends on xxxx pancreatic enzymes. Dietary B12 will remain bound to R protein in pts with pancreatic insufficiency (which is therefore a cause of B12 deficiency)

Answer 231

via cubilin receptor

Answer 232

only B12 deficiency can cause neuro issue (subacute degeneration of spinal cord); folate doesn't affect neurologic system in such a way

Answer 233

patient very unlikely to have significant degree of haemolysis.

Answer 234

b) extravascular haemolysis a) intravascular- positive urinary haemosiderin

Answer 235

severe valve disease)

Answer 236

4 degrees)

Answer 237

can be diagnosed only on DNA studies (electrophoresis for Beta-thal)

Answer 238

what blood disorder to you see in SE Asia? Mediterranean? Africa? SE Asia - alpha thal

Answer 239

high affinity for oxygen

Answer 240

so the gene itself is still -partially - functional)

Answer 241

doesn't correlate well. Need annual cardiac MRI to check iron burden on organs.

Answer 242

helps increase HbF levels & prevent crisis by increased Hb O2 binding capacity

Answer 243

hypergranular promyelocytes = ? APML

Answer 244

JAK2 mutation testing to look for essential thrombocytosis

Answer 245

there's just too many of them

Answer 246

and not enough of them

Answer 247

fludarabine

Answer 248

what's the biggest predictor of progression to MM? Size of the myeloma protein

Answer 249

when does engraftment usually occur? Day 15-30

Answer 250

Skin 90%. Then liver & gut. These three main sites are involved in GVHD occuring before Day 100 of allograft.

Answer 251

usually p/w cholestatic LFTs. DDx: veno-occlusive disease

Answer 252

Chronic inflammation.

Answer 253

and what % of ET? PRV - 95%

Answer 254

Favourable

Answer 255

Both are unfavourable; they'll do poorly. Need aggressive post-remission therapies

Answer 256

It's molecular targeted therapy at tyrosine kinase, added on to chemoTx, and has drastically improved prognosis of CML

Answer 257

Subtype of MDS. This type is responsive to lenalidomide.

Answer 258

Duodenal enterocytes

Answer 259

Type 1 - major binding port for iron, found on most cells. Binds transferrin 30x stronger than TfR2.

Answer 260

It's a storage facility for iron. Ferritin consists of an apoprotein shell with light & heavy chain subunits, which surround a core of iron atoms.

Answer 261

Cells excrete the same amount of ferritin storage units into the blood stream as they currently have inside them, and so checking the ferritin levels in the blood gives us an indication of how many ferritin 'storage units' there are within the cells, and from there, we can guess what amount of iron is present in the cell

Answer 262

Iron in cells.

Answer 263

Hepcidin causes internalisation of ferroportin, and so iron has no way of leaving the cell (it's only exit is via ferroportin). When body has low iron in storage, hepcidin expression is reduced (to allow ferroportin to stay on cell membrane & get iron out of cell into blood); and vice versa

Answer 264

Lymphocyte predominant

Answer 265

False - worse prognosis

Answer 266

As per NEJM 1998

Answer 267

Cyclophosphamide - causes cross-linking of DNA. S/Es: haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

Answer 268

Lung fibrosis

Answer 269

Cardiomyopathy

Answer 270

Vincristine

Answer 271

a) CML - t(9:22) - Philadelphia chromsome; BCR-AbL

Answer 272

Oral steroids; if not resolving, try immunosuppressive therapy (ciclosporin, infliximab)

Answer 273

AID, eg SLE

Answer 274

Neoplasia, eg lymphoma

Answer 275

Aka Osler-Weber-Rendu syndrome, is an AD condition characterised by multiple telangiectasia over skin / MMs. If you meet 2/4 of following = 'possible' diagnosis, if you meet 3/4 or 4/4 = 'definite' diagnosis. 1) Recurrent, spont. epistaxis. 2) Telangiectases (lips, mouth, fingers, nose). 3) AVMs in GIT, hepatic, cerebral, spinal, lungs. 4) FHx (1st degree relative) with HHT

Answer 276

Parvovirus

Answer 277

Acquired disorder leading to haemolysis of haematologic cells, thought to be due to increased sensitivity of cell membranes to complement due to lack of glycoprotein glycosyl-phosphatidylinositol

Answer 278

CD59 & CD55 on flow cytometry

Answer 279

- Haemolytic anaemia

Answer 280

RC cytoskeleton is deformed; no longer biconcave disc shape but rather sphere-shaped. This reduces RC survival --\> destroyed by spleen

Answer 281

Hereditary spherocytosis

Answer 282

Osmotic fragility test

Answer 283

Male (X-linked recessive)

Answer 284

Heinz bodies

Answer 285

Spherocytes (round, lack of central pallor)

Answer 286

Measure enzyme activity of G6PD

Answer 287

False. Not a/w polycythemia. Usually blood tests show raised ferritin & iron, a/w transferrin saturation \> 60% and a low total iron binding capacity

Answer 288

Dehydration

Answer 289

Philadelphia chromosome GOOD in CML, but BAD in AML & ALL

Answer 290

c-myc, usually t: 8:14

Answer 291

Burkitt's lymphoma

Answer 292

UFH - activates antithrombin III. Inhibits thrombin, factors Xa, IXa, XIa, XIIa

Answer 293

UFH - APTT

Answer 294

Immune mediated-antibodies, which activate platelets. This results in low platelet count (\>50% reduction), (however HITs paradoxically is a prothrombotic condition).

Answer 295

Imatinib = tyrosine kinase inhibitor. Used in CML. Specifically inhibits the tyrosine kinase associated with the BCR-ABL defect.

Answer 296

Imatinib is FIRST LINE TREATMENT

Answer 297

B-cells (CD 19 positive)

Answer 298

1) Partial reduction in vWF (80% of pts, AD)

Answer 299

Desmopressin (DDAVP) raises level of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

Answer 300

Parietal cells

Answer 301

Terminal ileum

Answer 302

Pernicious anaemia

Answer 303

Cytogenetics (although gene-expression profiling, WCC at diagnosis, immunophenotyping, LDH are also used to help prognosticate)

Answer 304

Antithrombin III deficiency - heparin works by enhancing its action.

Answer 305

High dose prednisolone

Answer 306

Increased megakaryocytes

Answer 307

Glycoprotein IIb-IIIa complex

Answer 308

Oral PNL (80% of pts respond)

Answer 309

Due primarily to increased osteoclastic bone resorption caused by local cytokines (IL1, TNF) released by myeloma cells

Answer 310

All of them

Answer 311

IgG and IgA

Answer 312

Uncommon, seen in old men. Lymphoplasmacytoid malignancy, characterised by secretion of monoclonal IgM paraprotein. Features: weight loss, hyperviscosity / DVTs, hepatosplenomegaly, LNs, cryoglobulinemia eg Raynaud's

Answer 313

Fludarabine

Answer 314

TTP due to abnormally large and sticky multimers of vWF which cause plts to clump within vessels. This is due to a deficiency of ADAMTS13, which normally breaks down large multimers of vWF.

Answer 315

Myelofibrosis.

Answer 316

Hyposplenism, eg post splenectomy

Answer 317

Iron defiency

Answer 318

Intravascular haemolysis

Answer 319

Antiphospholipid syndrome

Answer 320

Clexane. Less bleeding risk than heparin.

Answer 321

Hydroxyurea

Answer 322

APC resistance is due to mutated FVL.

Answer 323

Heterozygote - 5x increased risk of VTE

Answer 324

It binds to the urotoxic metabolites produced by cyclophosphamide, which reduces then the incidence of haemorrhagic cystitis

Answer 325

True. Works by cross-linking DNA.

Answer 326

Plasma exchange first-line.

Answer 327

Transferrin saturation

Answer 328

Perl's stain = iron; pt has haemochromatosis

Answer 329

Transferrin saturation - high

Answer 330

10% at 5 yrs;

Answer 331

True; a raised level implies poor prognosis

Answer 332

Hodgkin's lymphoma

Answer 333

Ann-Arbor staging of Hodgkin's lymphoma

Answer 334

Nodular sclerosing

Answer 335

Myelofibrosis or AML

Answer 336

Venesection - first line treatment

Answer 337

Gen pop = use transferrin saturation (better than ferritin level)

Answer 338

Increase / enhances warfarin, ie expect an increased INR with concommitant use of warfarin

Answer 339

Tend towards thrombocytosis

Answer 340

Aplastic anaemia

Answer 341

Bleeding - vWF

Answer 342

False. First line is a trial of oral PNL; 80% of pts respond. If not responding, do splenectomy, +/- IVIg +/- immunosuppressive drugs

Answer 343

Thymomas are the most common tumour of the anterior mediastinum Associated with myasthenia gravis (30-40% of patients with thymoma) red cell aplasia dermatomyositis also : SLE, SIADH

Answer 344

EBV: Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma HTLV-1: Adult T-cell leukaemia/lymphoma HIV-1: High-grade B-cell lymphoma

Answer 345

High - ALKYLATORS - cyclophosphamide - chlorambucil - procarbazine - melphalan Low Antimetabolites Vincristine Bleomycin