Haematology including malignancy + blood transfusion Flashcards

Question

What age group is commonly affected by AML?

Answer 1

median age of onset is 70 increasingly common with age

Answer 2

* Myelodysplastic syndrome: blood disorders affecting haematopoiesis; those with excessive blasts are at risk of AML * Radiation exposure- survivors of atomic blasts in Hiroshima & Nagasaki * Previous chemo * Toxins- certain insecticides

Answer 3

* Down syndrome * Congenital neutropenia * Fanconi anaemia- rare genetic disorder, inherited BM failure

Answer 4

**Marrow failure leading to** anaemia, neutropenia, thrombocytopenia **Tissue infiltration leading to l**ymphadenopathy, hepatosplenomegaly, bone pain, gum hypertrophy, skin deposits, testicular enlargement **Leucostasis leading to** altered mental status, headache, dyspnoea, visual changes

Answer 5

Bone marrow aspirate and biopsy is required for formal diagnosis of AML. * Hypercellular BM * Myeloid blast count \> 20% * Immunophenotyping identifies the lineage of cells- sent to cytogenetics & flow cytometry Bloods * Normochromic normocytic anaemia * + thrombocytopenia * Total WCC often increased; leucopenia can also be encountered * Reduced reticulocyte counts * Circulating myeloblasts are found * Clotting screen as may have DIC in the promyelocytic variant of AML * LDH may be raised as a non-specific marker of increased cell turnover Blood film * Increased number of blast cells * +/- Auer rods Imaging * CXR * CT CAP * CT/ MRI head Other * LP if CNS concerns

Answer 6

Supportive management: * Transfer to specialist centre + enrol onto clinical trial where possible * Monitor for infections, coagulopathy and treat accordingly- prophylactic abx, anti-fungals & anti-virals, blood transfusions * Insertion of central venous cannula * Treat any fevers promptly Definitive management: * National trials around the country * Age up to 24- TYA service * Principles of treatment: * INDUCTION - An induction regime consisting of cytarabine, daunorubicin and gemtuzumab ozogamicin (GO) * CONSOLIDATION - A consolidation regime consisting of intermediate-dose cytarabine (IDAC) +/- gemtuzumab ozogamicin

Answer 7

Adverse prognostic factors: age 60+, poor performance status, multiple significant co-morbidities, previous haem disorders/ dysplasia, previous chemo or RT, certain disease subtypes

Answer 8

Philadelphia chromosome (22) causes abnormally activated tyrosine kinase: BCR-ABL1 protein

Answer 9

**_Symptoms_**: * **Hypermetabolism**- fatigue, wt loss, night sweats * **Anaemia**- fatigue, breathless, angina, pallor * **Thrombocytopenia**- petechiae, nose bleeds, bruising * **Splenomegaly**- early satiety, abdo pain * **Bone pain** * **Leucostasis**- headache, breathlessness, visual changes, priapism * **Hyperuricaemia-** gout, renal impairment **_Signs_**: hepatosplenomegaly, lymphadenopathy, leucostasis

Answer 10

Bloods * FBC- raised WCC (leucocytosis)- basophils and commonly eosinophils * Normochromic normocytic anaemia * Platelet may be high, low, normal Blood film * Immature & mature myeloid cells * Various stages of granulopoiesis including promyelocytes, myelocytes, metamyelocytes, and band and segmented neutrophils Bone marrow * Biopsy used for staging & as material for cytogenetics- chromosome 22 looked for * Marrow tends to be hypercellular with myeloid hyperplasia in chronic phase disease

Answer 11

Tyrosine kinase inhibitors- directly block the enzyme created by BCR-ABL1, tyrosine kinase. Imatinib * First generation TKI * 400mg daily * SE: N&V, oedema, cramps, rashes, GI symptoms, headache, fatigue * Monitoring response: BCR-ABL1 mRNA levels in blood- real-time PCR (or BM sample, more invasive) Dasatinib, nilotinib are examples of others. All these 3 TKIs are used in the treatment of chronic phase CML. Allogenic stem cell transplant considered if this fails. Accelerated phase/ blast crisis: treat pts as part of clinical trial, use 2^nd gen TKI +/- intensive chemo, +/- allo-SCT

Answer 12

Diagnosis age 15-64: 90% 5 year survival Age 65+: 40% 5 year survival

Answer 13

***_Lymphoma_*** is a haematological malignancy arising from lymphoid tissue. They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma: * Hodgkin lymphoma (HL): * Characterised by the presence of Hodgkin/Reed-Sternberg cells (large, multinucleated cells). * Further categorised as ***classical Hodgkin's lymphoma*** (nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted) and ***nodular lymphocyte-predominant Hodgkin's lymphoma***. * Non-Hodgkin lymphoma (NHL): * Reed-Sternberg cells are not seen in NHL. * There are more than 60 subtypes * B-cell or NK/T-cell in origin * B-cell lymphomas are more common accounting for around 80%, though there is significant geographic variation * NHLs are more common than Hodgkin lymphoma, accounting for around 80-85% of lymphomas.

Answer 14

Classical type: 95% of all cases 1. Nodular sclerosis- most common subtype, 70% 2. Mixed cellularity- 20% 3. Lymphocyte-rich- 5%, best prognosis 4. Lymphocyte-depleted- \<1%, worse prognosis Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)- very rare, 5% of all HL, seen in black males

Answer 15

Hodgkin/ Reed-Sternberg cells (HRS cells)

Answer 16

* Any age * Rare in ch. + peak incidence in young adults * 2:1 male * EBV * Smoking * HIV * Immunosuppression

Answer 17

* Gradual lymphadenopathy- painless, firm, enlarged, rubbery, asymmetrical, discrete superficial lymph nodes, common in neck * B symptoms- fever, night sweats, unexplained wt loss \>10% in 6mnths * Mediastinal mass- SoB, cough, SVCO * Hepatosplenomegaly * Fever- continuous/ cyclical * Pruritis- often severe- 25% cases * Alcohol-induced pain Other constitutional symptoms- malaise, fatigue, profuse sweating esp. at night, anorexia, cachexia

Answer 18

Excision biopsy of affected lymph nodes- preferred to FNA or core biopsy - immunophenotyping of HRS cells

Answer 19

FBC: * - normochromic normocytic anaemia * - neutrophilia, eosinophilia common * - advanced disease: lymphopenia * - platelet count normal or high in early disease, reduced in later stages * - ESR and CRP raised- good for monitoring disease progression * - LDH high * - U&E, LFTs Imaging: * CXR * PET CT- staging * CT neck, CAP scan- retroperitoneal nodes * MRI brain, liver Other ix * LP & CSF analysis in suspected CNS disease * Echo- assess cardiac function if considering doxorubicin chemotherapy * Pulmonary function tests- if considering bleomycin chemotherapy * BM biopsy- if uncertain dx

Answer 20

Lugano staging system 1. Node involvement in 1 node area 2. 2 or more lymph nodal areas, on 1 side of the diaphragm Includes splenic disease 3. Lymph nodes above + below diaphragm involved 4. Involvement outside the lymph nodal areas- diffuse disease in BM, liver and other sites The stage number is followed by A or B: 1. Absence of B symptoms 2. Presence of B symptoms *‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, \>10% in 6 months)*

Answer 21

Chemotherapy & RT or combination of both Stage I and IIA: radiotherapy alone Stage III, IV, I/II B, bulky disease: cyclical chemotherapy- ABVD widely used (Adriamycin, bleomycin, vinblastine, darbazine)

Answer 22

To reduce the risk of transfusion-associated graft-versus-host disease

Answer 23

* Limited disease: stage I and II- 90% survive 5 years * Advanced disease: III and IV- 75-90% survive 5 years

Answer 24

* Developing cancer secondary to radiotherapy- lung and breast cancer * Intestinal complications * Sterility/ infertility * Mediastinal radiation effectsà coronary artery disease or pulmonary disease

Answer 25

Large group of clonal lymphoid tumours * 85% B cell * 15% T or NK cell origin * No Reed Sternberg cells as in HL * NHLs are more common than HL, they account for 80-85% of lymphomas

Answer 26

* EBV: Burkitt lymphoma * HIV: high grade B cell lymphoma * Hep C: marginal zone lymphoma * H pylori: gastric lymphoma (MALT) * Malaria: Burkitt lymphoma

Answer 27

Most common symptom: lymphadenopathy * Constitutional symptoms- night sweats, fever, weight loss * Anaemia * Hepatosplenomegaly * Pruritis * Primary CNS lymphoma-neuro symptoms eg headache, confusion, seizures, coma * Primary cutaneous lymphoma-rashes, plaques, ulcers * Primary GI tract lymphoma- abdo pain, nausea, obstruction, haemorrhage As an emergency such as * Superior vena cava obstruction (SVCO) * Cord compression * Hypercalcaemia * Tumour lysis syndrome * Neutropenic sepsis

Answer 28

Bloods- * FBC * Anaemia, neutropenia, thrombocytopenia * U&Es, LFTs, ESR, bone profile, LDH, uric acid, viral screen Imaging- * CXR * CT neck, CAP- assessing nodes & solid organs (liver + spleen) * PET CT- some lymphomas may not be PET avid * MRI brain * Testicular USS- suspecting testicular lymphoma * Bone scan Other- * Excision biopsy of affected lymph nodes or tissue is normally required * Needle core biopsy may be considered in those unfit for excisional biopsy, however if this fails to produce a sufficient sample excisional biopsy will have to be reconsidered * Bone marrow biopsy- BM involvement found in low-grade malignant lymphomas

Answer 29

R-CHOP is the common chemotherapy regimen used * Rituximab- mab against CD20 (antigen found on surface of B cells) * SE: infusion reactions, hep B reactivation, mucocutaneous reactions* * Cyclophosphamide- alkylating agent, inhibits DNA synthesis via cross-linking DNA * SE: BM suppression, infertility, TCC of bladder* * Doxorubicin- anthracycline inhibits topoisomerase II à inhibition of DNA/ RNA synthesis * SE: cardiomyopathy, myelosuppression, skin reactions* * Vincristine- inhibits microtubule formation by binding tubulin * SE**: peripheral neuropathy,** bladder atony* * Prednisolone

Answer 30

30+ types, classified based on B or T lymphocyte is involved ***_Types of B-cell NHLs:_*** ***_Low-grade NHLs: indolent but often incurable_*** * Follicular lymphoma - 2^nd most common B-cell NHL - t(14,18) * MALT lymphoma * Small cell lymphocytic lymphoma - same morphology, immunophenotype + cytogenetics as CLL, less than 5 x 10 ^9/L peripheral blood B cells & no cytopenias due to BM involvement. Often elderly pts & no treatment required * Marginal zone B cell lymphoma ***_High-grade NHLs: aggressive but often curable_*** * Diffuse large B cell lymphoma (DLBCL) -most common NHL * Burkitt’s lymphoma -commonly affects children, often males -mutation to c-myc proto-oncogene btwn chromosomes 8 and 14 * Lymphoblastic lymphoma B or T cell, merge clinically w/ ALL * Mantle cell lymphoma -poor prognosis ***_T cell NHLs:_*** * Adult T-cell leukaemia/ lymphoma associated with HTLV-1 infection

Answer 31

= high white cell count Infections * CMV * Hep B, C * TB ALL or CLL Hypothyroidism

Answer 32

Flow cytometry- shows markers on cells

Answer 33

Acute * Haemorrhage during or immediately after * Pulmonary atelectasis, pneumonia * Gastric ileus * Acute pancreatitis * Thrombocytosis and leucocytosis Short term * OPSI- overwhelming post-op infection * DIC * pulmonary infection * DVT * Spleno-portal throbosis- fever, abdo discomfort Long term * OPSI +/- DIC * Pulmonary infection * VTE * Pulmonary HTN * Enhanced atherosclerosis * Arterial thrombosis

Answer 34

* How long has it been there? Has it changed? * Does it hurt? Swallowing okay? * Triggers * Associated viral illness? * Ever happened before? Any other lumps? * B symptoms – wt loss, fever * Differentials: viral illness eg glandular fever (esp young age- sweats, aches, wt loss), TB, lymphoma (smooth, painless), secondary lump from gastric cancer, oesophageal cancer, thyroglossal cyst, also ct disorders eg SLE, RA Features * Features of the lymph node * Tender/ non-tender (infection, Hodgkin lymphoma when drinking alcohol- tender) * Mobile * Enlarged, rubbery- malignancy * Hard, firm irregular, tethered to other structures- associated with mets? * Other lymph nodes- H&N, axilla, groin * Breathlessness, dizziness- anaemia * Rashes, clubbing * Bruising- thrombocytopenia * Pyrexia- B symptoms? * Spleno-megaly- spleen is like a massive lymph node, part of RES * Hepatomegaly possible

Answer 35

Excision biopsy- taking it all out- this is best Core biopsy- takes a part- good if things are inaccessible but get much less tissue

Answer 36

Uses- * Polycythaemia vera * Essential thrombocythaemia * Chronic myeloid leukaemia Consderations- * Teratogenic effects * Myelosuppression * Kidney and liver function

Answer 37

* Mets of primary solid malignancy * Infections * Autoimmune disease eg SLE, RA * Graft versus host disease * Sarcoidosis * Drugs eg phenytoin, isoniazid, allopurinol * Covid vaccine

Answer 38

* Fatigue * N&V * Diarrhoea and constipation * Hair loss * Infections * Anaemia * Bruising and bleeding * Mucositis * Loss of appetite * Skin and nail changes * Insomnia * NEUTROPENIC SEPSIS

Answer 39

Multiple myeloma refers to a malignant disorder of plasma cells (mature B lymphocytes) * accummulation of plasma cells in bone marrow * presence of monoclonal antibody in serum +/- urine * associated tissue damage

Answer 40

Innate immunity * First line of defence * Cells- phagocytes, dendritic cells * Molecules- complement, cytokines * Recognition of PAMPs stimulates pro-inflammatory response + activates adaptive immunity Adaptive immunity * Antigen specificity: it can detect almost an unlimited number of antigens with high accuracy * Delayed onset: takes 2-4 days to mount an adaptive immune response (on first encounter) * Immune memory: rapidly protective on re-exposure to a foreign antigen * Primary cell: lymphocytes

Answer 41

* Abnormal monoclonal proliferation of plasma cells * The plasma cells synthesise & secrete a monoclonal protein = also known as **M protein** or **paraprotein** * The paraprotein can be: * **Immunoglobulin** - usually **IgG** or **IgA** * Immunoglobulin + light chain * **Light chain only** = immunoglobulin-free light chains * Either **kappa** or **lambda** light chain proteins * The normal kappa:lambda serum ratio is 0.6; this is skewed by either an increase in kappa or lambda light chains * These light chains are synthesised by plasma cells which have not been paired with a heavy chain * Light chains can pass through the glomerulus, saturate the reabsorption mechanism, and appear in the urine as **Bence-Jones protein**

Answer 42

SLiM CRAB * **S**ixty % plasmacytosis * **Li**ght chains I/U \> 100 * **M**RI 1 or more focal lesion * **C**alcium elevation * **R**enal insufficiency * **A**naemia * **B**one disease

Answer 43

3 main mechanisms- * The most common cause of kidney failure in the myeloma patient is due to the paraprotein secretion * Bence Jones protein is deposited in renal tubules and leads to cast nephropathy leading to renal failure * Amyloid deposition * Systemic amyloid light chain (AL) amyloid disease * Caused by deposition of monoclonal light chains produced from a clonal plasma cell proliferation * Involvement of heart, peripheral nerves, kidneys * pts present w/ HF, macroglossia, peripheal neuropathy, CTS, RF * Increased bone loss - hypercalcaemia - dehydration - AKI

Answer 44

* Amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid * In addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P * The accumulation of amyloid fibrils leads to tissue/organ dysfunction * Further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments) * **_Clinical features_** * Renal disease: commonly presents as nephrotic syndrome * Cardiac disease: HF, syncope, infarction due to deposits in coronary arteries * GI disease: hepatomegaly, splenomegaly, bleeding, constipation * Neurological disease: ischaemic stroke, neuropathy * **_Diagnosis_** * Congo red staining: apple-green birefringence * serum amyloid precursor (SAP) scan * biopsy of rectal tissue

Answer 45

**_Multiple myeloma_** * haematological malignancy characterised by plasma cell proliferation * It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells * Plasma cell acummulation in bone marrow, presence of monoclonal protein in serum +/- urine, and related tissue damage if symptomatic **_Smouldering myeloma_** = asymptomatic myeloma **_Monoclonal gammopathy of undetermined significance (MGUS)_** * Paraproteinaemia Differentiating features of MGUS from myeloma * normal immune function * normal beta-2 microglobulin levels * lower level of paraproteinaemia than myeloma (e.g. \< 30g/l IgG, or \< 20g/l IgA) * stable level of paraproteinaemia * no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease) **_Benign polyclonal hypergammaglobinaemia_** * Hypergammaglobulinemia, the overproduction of immunoglobulins by plasma cells, is broadly divided into monoclonal and polyclonal subtypes * Monoclonal paraproteins are typically associated with plasma cell neoplasms and B-cell lymphomas such as monoclonal gammopathy of undetermined significance (MGUS), plasma cell myeloma, primary amyloidosis, chronic lymphocytic leukemia and lymphoplasmacytic lymphoma

Answer 46

Monoclonal Gammopathy of undetermined significant * Often incidental finding * All 3 criteria are met: 1. Paraprotein in serum \<30g/L 2. Marrow clonal plasma cells \<10% 3. No features of myeloma end-organ damage/ lymphoma/ amyloidosis rate of progression estimated at 1% per year * Around 10% of patients eventually develop myeloma at 5 years, with 50% at 15 years * The evolution from MGUS to advanced disease may be abrupt. As a result, patients should be advised to obtain medical evaluation promptly if clinical symptoms occur

Answer 47

* Bone disease: * Widespread due to clonal proliferation in bone marrow * Bone pain- especially back ache reuslting from vertebral collapse * Lytic lesions on imaging * Pathological fractures * Impaired renal function: * \>50% have raised creatinine at diagnosis * Commonly due to light chain nephropathy (tubules blocked by light chain casts) * Anaemia: * Seen in \>90% at some point during disease course * Normal bone marrow destroyed by proliferation of malignant plasma cells * Renal disease - EPO deficiency * Hypercalcaemia: * MM-induced bone demineralisation * More common in active disease * At high levels (≥ 2.9 mmol/L) - emergency * Recurrent or persistent bacterial infection: * Suppression of normal plasma cell production * Deficient antibody production * Abnormal cell-mediated immunity * Neutropenia * Hypogammaglobulinaemia * Abnormal bleeding tendency: * Myeloma protein interferes w/ platelet function & coagulation factors * Thrombocytopenia may occur in advanced disease * Amyloidosis: 5% cases * Features such as macroglossia, carpal tunnel syndrome, diarrhoea * Hyperviscosity syndrome: 2% cases * Purpura, haemorrhages, visual failure, CNS symptoms, neuropathies, HF

Answer 48

* Bone pain, often in the lower back * Fatigue * Confusion, muscle weakness, constipation, thirst, and polyuria (due to hypercalcaemia) * Weight loss * Recurrent infection * Headache, visual disturbance, cognitive impairment, mucosal bleeding, and breathlessness (due to hyperviscosity of the blood) * Sensory loss, paraesthesia, limb weakness, walking difficulty, and sphincter disturbance (due to spinal cord compression)

Answer 49

* Normochromic, normocytic anaemia * Renal impairment * Hypercalcaemia * Raised erythrocyte sedimentation rate (ESR), plasma viscosity, serum protein, or globulin

Answer 50

* They are usually reabsorbed in PCT but large quantities mean they prescipitate out as casts * Cause tubular inflammation/ destruction * Causes AKI * Reduces EPO output from kidney * This can lead to anaemia

Answer 51

Bloods * FBC * Calcium * Plasma viscosity or ESR * U&Es, creatinine- assess renal function * Albumin- low in advanced disease * Serum β2-microglobulin- often raised- levels \<3.5 indicate better prognosis Very urgent serum electrophoresis, serum-free light chain assay, and Bence-Jones protein urine assessment (within 48 hours) for people over 60 years of age with hypercalcaemia or leukopenia, and a presentation consistent with possible myeloma Imaging * Whole body MRI as first-line imaging * Whole body low dose CT if MRI is unsuitable/ declined * Only consider skeletal survey as first-line if both MRI and CT are unsuitable or declined

Answer 52

‘Screening’ for myeloma involves looking for monoclonal antibodies, which are the secretion product of the malignant clones * **_Protein electrophoresis_**: quantitative test; tells us if there is an increase in number of antibodies * **_Immunofixation:_** qualitative test; tells us what type of antibody has increase ie is it a monoclonal antibody The issue with the above: protein electrophoresis assumes all myelomas secrete an intact antibody; however 20% myelomas secrete light chains only... * **_Serum free light chains_** (this has largely replaced the need for analysis of urine paraproteinaemia) * Looks at the amount of light chain unbound to heavy chains within the blood * Light chains are secreted in healthy individuals as plasma cells produce more light chains than heavy chains * Therefore, it is the ratio between the light chains kappa and lambda, which is the most important factor * Normal ratio is 0.6; a deranged ratio means either kappa or lambda are deranged * Urine electrophoresis

Answer 53

* **_Monoclonal antibody detection:_** protein electrophoresis & immunoglobulins, SFLCs +/- urine electrophoresis for Bence-Jones protein * **_Bone marrow infiltration:_** bone marrow aspirate and trephine with cytogenetics. BM plasma cells \>10% * **_Myeloma-related organ damage:_** FBC, U&Es, bone profile, imaging (whole body MRI or low-dose whole body CT if MRI not suitable). Skeletal survey (x-rays) only used if CT/MRI not possible Staging if confirmed myeloma: beta-2 microglobulin, albumin

Answer 54

* Age * Male * Black African ethnicity * FHx * Obesity

Answer 55

* Incurable: aim for periods of disease remission * Induction therapy: initial treatment option. Aim to induce remission. Usually combination of three drugs. Choice depends on high-risk features, co-morbidities and plan for ASCT. Example is VRd (Velcade - bortezomib / Revlimid - lenalidomide / dexamethasone - steroid) * Intensive therapy- for those \<65-70 * 4-5 courses of chemotherapy to reduce tumour burden * IV or oral chemotherapy cycles use cyclophosphamide, dexamethasone and thalidomide (CDT) * Stem cell collection & autologous SCT after high dose chemotherapy * High-dose melphalan +/- radiotherapy * Non-intensive therapy- for elderly pts * Melphalan with prednisolone, thalidomide or bortezomib- reducing tumour burden * Cyclophosphamide can be used as a single agent * Typically, paraprotein levels will fall, bony lesions will show an improvement and blood counts may improve * After a variable number of courses, there'll be a plateau phase where the paraprotein stops falling- at this point treatment is stopped & pt is regularly reviewed * After a variable period of time (often 18mnths), the disease escapes from the plateau with rising paraprotein & worsening symptoms * The disease becomes difficult to control as time progresses further chemo may be given

Answer 56

* Myeloma bone disease * Bisphosphonates for bony pain * Pamidronate, clodronate, zoledronic acid * Hypercalcaemia * Rehydration- isotonic saline * Diuretic * Corticosteroids * Bisphosphonate * Cord compression * Decompression laminectomy or irradiation * Corticosteroid therapy may help * Renal impairment * Rehydrate * Find out cause eg high calcium high urea * Dialysis * Anaemia * Transfusion * EPO * Peripheral neuropathy * Infection * Prophylactic abx and antifungals for recurrent infections * Hyperviscosity

Answer 57

* Bisphosphonates for main; suppress osteoclast activity * Radiotherapy to bone lesions can improve bony pain * Orthopaedic surgery can stabilise bones eg by inserting prophylactic intramedullary rod or treating fractures * Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain

Answer 58

* Stage I: median survival 62 months * Stage II: median survival 44 months * Stage III: median survival of 29 months * Other factors associated with a worse prognosis include high plasma cell counts, high levels of monoclonal antibody in blood/urine or development of complications (e.g. diffuse multiple bone lesions, marked anaemia, hypercalcaemia and renal impairment).

Answer 59

The spleen consists of red pulp- sinuses lined by endothelial macrophages & cords- and white pulp- similar structure to lymphoid follicles Functions- * Sequestration and phagocytosis – old/abnormal red cells removed by macrophages * Blood pooling – platelets and red cells can be rapidly mobilised during bleeding * Extramedullary haemopoiesis – pluripotential stem cells proliferate during haematological stress or if marrow fails (eg myelofibrosis) * Immunological function – 25% of T cells and 15% of B cells are present in the spleen * More re infection

Answer 60

* Back pressure- **portal hypertension** in liver disease * Over working red pulp- **haemolytic anaemia** * Over working white pulp- *infection* * Malaria * Schistosomiasis * HIV * Glandular fever (EBV) * Reverting to what it used to do- **extramedullary haemopoiesis** * ****This occurs in disorders such as primary myelofibrosis or in chronic severe haemolytic and megaloblastic anaemias * May result either from reactivation of dormant stem cells within the spleen or homing of the stem cells from the bone marrow to the spleen * Expanding as infiltrated by cells which shouldn’t be there * **Cancer** cells of blood origin eg leukaemia, lymphoma * Other cancer metastases * Expanding as infiltrated by other material * **Gauchers disease**- a defect in the beta-glucosidase enzyme which catalyses the breakdown of glucocerebroside (a constituent of red and white blood cell membranes), causes glucocerebroside to accumulate in fibrils * **Sarcoidosis**

Answer 61

Causes of hyposplenism- * Disease which destroy spleen tissue * SCA * Coeliac disease * Splenectomy is the most common cause of hyposplenism * Inflammatory bowel disease * Splenic arterial thrombosis Blood film- * Howell-Jolly bodies- basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes Management- * Preventing infection * Inform pt of risk & tell them to carry a card- include counselling of increased risk of travel * Prophylactic oral penicillin for life * Erythromycin if allergic to penicillin * Vaccination * Pneumoccous * Haemophilus * Meningococcus * Influenza

Answer 62

* Most diagnosed after the age of 55 * But it is one of the more common cancers in young people * Age group 8-84 most commonly affected

Answer 63

* Lugano staging system is used * Describes the anatomical distribution of disease and is of both prognostic & therapeutic importance 1. Node involvement in 1 node area 2. 2 or more lymph nodal areas, on 1 side of the diaphragm Includes splenic disease Stage II bulky: bulky disease refers to disease \> 10cm 3. Lymph nodes above + below diaphragm involved 4. Involvement outside the lymph nodal areas- diffuse disease in BM, liver and other sites The stage number is followed by A or B: 1. Absence of B symptoms 2. Presence of B symptoms *‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, \>10% in 6 months)*

Answer 64

* Most common form of NHL * More common in men than women, appears to present at younger age in those of black ethnicity * Rapidly enlarging mass, commonly in neck, abdo, mediastinum * B symptoms * Disease in mediastinum à SVCO

Answer 65

* B cell NHL, second most common form of NHL * Often presents insidiously, gradual lymphadenopathy (painless) * B symptoms

Answer 66

* High grade, rapidly proliferating, B-cell NHL, commonly affects children * Relatively uncommon in the UK * Frequently affects males * Strong association with EBC and follows the distribution of malaria * Also associated with AIDs or other conditions leading to immunosuppression * Endemic Burkitt’s classically presents with rapidly enlarging tumour in the jaw of a child, can also present with lymph nodes in neck or abdo masses * Sporadic Burkitt’s often affects ileocaecal valve, can present as BO * Fever, weight loss, night sweats

Answer 67

* Low platelet count * \<150 x 10⁹ /L * Increases the risk of bleeding * Avg platelet life span is ~5 days à even brief disruptions to platelet production or survival can result in thrombocytopenia

Answer 68

* These can be broken down into three broad categories: * Reduced platelet production * Viral infections eg HSV, CMV, EBV * Chemotherapy- BM toxicity, inhibits production of platelets * Aplastic anaemia * Haematological malignancy- leukaemia, crowding of BM by malignant cells * B12 and folate deficiency à macrocytic anaemia, thrombocytopenia * Excess alcohol intake à BM toxicity, liver cirrhosis * Congenital conditions- eg Fanconi’s anaemia * Reduced platelet survival * Immune related- ITP, SLE, RA, sarcoidosis * Non-immune related- * Medications eg heparin, carbamazepine, ibuprofen * Splenomegaly * Haemolytic uraemic syndrome * TTP * Dilution of platelet numbers * Pseudo thrombocytopenia- platelets clump and give a false low reading in the auto-analyser

Answer 69

* Immune mediated reduction in platelet count * Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex * Ix- antiplatelet autoantibodies (usually IgG), BM aspiration- megakaryocytes in marrow, should be carried out before steroid mx to rule out leukaemia * Mx- oral prednisolone, splenectomy, IV immunoglobulins, immunosuppressive drugs eg cyclophosphamide

Answer 70

* Tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues * Features- rare, typically adult females, fever, fluctuating neuro symptoms (micro-emboli), microangiopathic haemolytic anaemia, thrombocytopenia, renal failure * Causes- post infection, pregnancy, drugs, tumours, SLE, HIV

Answer 71

* Plasma exchange * Steroids * Rituximab

Answer 72

* ABO blood group classification is based on the presence or absence of antigens A and B, which are carried on the surface of red cells * Type A blood type: type A antigen on surface of red cells, and antibodies against type B red cells in serum à will destroy type B blood if it is injected into their blood * Type O can be injected into persons with type A, B or O blood * Type AB blood can receive type A, B or O

Answer 73

* Alongside the ABO system, the rhesus system is the most important antigen on RBC * The D antigen is the most important antigen of the rhesus system * Around 15% mothers are Rhesus negative: Rh -ve blood given to Rh -ve pts * If a Rh -ve mother delivers a Rh +ve child a leak of fetal RBC may occur, causes anti-D IgG antibodies to form in mother, in later pregnancies these can cross placenta and cause haemolysis in fetus (can also occur in first pregnancy) * Rh positive or Rh negative blood given to Rh positive pts * Prevention: test for D antibodies in all Rh -ve mothers at booking * Give anti-D to non-sensitised Rh-ve mothers at 28 and 34 weeks- this neutralises any RhD +ve antigens that may have entered the mother’s blood during pregnancy, so the mother’s blood won’t produce antibodies

Answer 74

* Allo-antibodies are immune antibodies that are only produced following exposure to foreign RBC antigens * Haemolytic disease of the newborn occurs due to presence of red blood cells alloantibodies in the maternal plasma during pregnancy * Those antibodies cross the placental barrier and enters the fetal bloodstream, binds to erythrocyte antigens and destroy fetal erythrocytes

Answer 75

* Rhesus haemolytic disease * ABO haemolytic disease * Hereditary spherocytosis * Glucose-6-phosphodehydrogenase

Answer 76

* Group and screen is required whenever a pt may require a blood transfusion eg surgical risk, haemorrhage, anaemia, determines their ABO and RhD blood group and screens for any atypical antibodies * Non-urgent cases, samples should be sent at least 24 hrs beforehand * Urgent cases, can be completed within 1 hr * If blood is required urgently and there is no valid group and save, a full serological crossmatch takes approx. 40 mins * Cross match involves physically mixing of pt’s blood with donor’s blood to see if any immune reaction occurs * Cross match is performed if blood loss is anticipated

Answer 77

* Thresholds for transfusion: (this is not for major haemorrhage or chronic anaemia needing regular transfusions) * Pt w/o ACS: 70 g/L * Target after transfusion: 70-90 * Pt w/ ACS: 80 g/L * Target after transfusion: 80-100 * Single unit red blood cell transfusions

Answer 78

* Pts w/ thrombocytopenia & are bleeding: \<30 x10⁹ per L * Use higher thresholds in severe bleeding or bleeding in critical sites such as CNS (including eyes) * Pts who are not actively bleeding or having invasive procedures or surgery and who don’t have chronic bone marrow failure, autoimmune thrombocytopenia, heparin-induced thrombocytopenia, TTP: \<10 x10⁹ per L * Prophylactic platelet transfusions to raise platelet count to 50 x10⁹ per L for pts having invasive procedures or surgery

Answer 79

* FFP is prepared from single units of blood and contains clotting factors, albumin and immunoglobulin * Only consider FFP for pts with clinically significant bleeding but not major haemorrhage if they have abnormal coagulation test results (eg PT time ratio \> 1.5) * Do not offer FFP to correct abnormal coagulations in pts with no bleeding or who need reversal of a vitK antagonist * Cryoprecipitate is formed from supernatant FFP, rich source of factor VIII and fibrinogen * Consider cryoprecipitate transfusions for pts w/o major haemorrhage who have both of the following: * Clinically significant bleeding, and * Fibrinogen level \< 1.5 g/L * Do not offer cryoprecipitate transfusions to correct fibrinogen level in pts who aren’t bleeding and are not having invasive procedures or surgery with a risk of bleeding * Offer immediate prothrombin complex concentrate transfusions for the emergency reversal of warfarin anticoagulation in pts w/ either: * Severe bleeding, or * Head injury w/ suspected intracerebral haemorrhage

Answer 80

* Stop warfarin * Vitamin K à reversal within 4-24 hours * IV takes 4-6hrs * Oral 24 hrs * Human prothrombin complex à reversal within 1 hr * Bereplex 50 u/kg * Rapid action but factor 6 short half life, hence give vit K instead * FFP- less commonly used now, need to give at least 1L fluid in 70kg person (not appropriate in fluid overload), need blood group * Only use if human prothrombin complex is not available

Answer 81

* Blood transfusion from 1^st/2^nd degree relatives * Congenital immunodeficiency states * Autologous/ allogenic haematopoietic progenitor cell transplant (BM or peripheral) * Hodgkin’s disease (lifelong) * Specified in particular treatment protocol

Answer 82

* Neonates * Granulocyte components for CMV seronegative pts * Adult & paediatric CMV seronegative allogenic haematopoietic progenitor cell transplant (BM or peripheral) recipients * Pregnant women requiring transfusions during pregnancy (not labour/ delivery)

Answer 83

* Loss of more than 1 blood volume within 24 hours (around 70mL/kg, \>5L in a 70kg adult) * 50% of total blood volume lost in \< 3 hours * Bleeding in excess of 150 mL/minute

Answer 84

* ABCDE approach * Give appropriate warmed IV crystalloid bolus * Red cell transfusion is necessary if 30-40% blood volume loss and raid loss of \>40% is immediately life threatening * Peripheral blood haematocrit & Hb concentration can be misleading early after major acute blood loss, the initial diagnosis of major haemorrhage requiring transfusion should be based on clinical criteria & observations * For immediate transfusion, issue group O red cell after samples are taken for blood grouping & cross matching * Females \<50 years old should receive RhD negative red cells to avoid sensitisation * ABO group specific red cells can usually be issued within 10 mins of a sample arriving in the lab * Fully crossmatched blood within 30-40 mins * Immediate haemorrhage control measures eg * Direct pressure on wounds/ nose if epistaxis * Pelvic binder for suspected unstable pelvic # * Tourniquet where indicated * Consider antifibrinolytic measures and reverse any anticoagulation * Arrange cell salvage where available * Senior makes decision to active major haemorrhage protocol- dial 2222

Answer 85

* Clinically obvious severe traumatic bleeding or collapse * Haemorrhagic shock eg systolic BP \<70 initially or \<90 after fluid bolus * \>4 units red cells transfused within an hour AND similar further needs anticipated * Bleeding rate 150mL/min * 50% total blood volume loss in 3hrs

Answer 86

* For pts before surgery- * IV/ oral iron * Cell salvage * Tranexamic acid (anti-fibrinolytic)

Answer 87

* Reactions * Acute haemolytic reaction/ ABO incompatibility * TRALI * Fluid overload * Anaphylaxis * Allergy- urticaria, itch * Infections * Viral- HIV, hep B, hep C, CJD * Bacteria- contamination

Answer 88

* Immunological * ABO mismatch * Delayed haemolytic transfusion reactions * Transfusion-related acute lung injury (TRALI) * Anaphylaxis * Non-haemolytic febrile transfusion reactions * Non-immunological * Transfusion-associated circulatory overload (TACO) * Transmission of infection

Answer 89

* Acute haemolytic transfusion reaction is the result of a mismatch of blood group (ABO) which causes massive intravascular haemolysis * This is usually the result of RBC destruction by IgM-type antibodies * Symptoms begin minutes after the transfusion is started * Features: strong feeling of dying, fever, hypotension, agitation breathing difficulty, muscle ache, nausea, chest/ abdo/ back pain

Answer 90

* Immediately stop the blood transfusion * Confirm diagnosis, check identity of pt/ name on blood product, send blood for direct coombs test, repeat typing and cross-match * Supportive care- generous fluid resuscitation with saline solution * Monitor UO/ catheterise * Maintain UO at 100mL/hr * Give furosemide if UO falling in consultation w/ renal registrar * Treat any DIC: Anti-DIC treatments * Inform Hospital Transfusion Department immediately

Answer 91

* Disseminated intravascular coagulation * Renal failure

Answer 92

* Febrile reactions due to white blood cell HLA antibodies, often the result of sensitisation by previous pregnancies or transfusions * Paracetamol may be given * Restart infusion at slower rate and take more frequent clinical observations

Answer 93

* Pulmonary oedema * Hypertension

Answer 94

* Slow or stop transfusion * Consider IV loop diuretics - furosemide 40-80mg IV and O2

Answer 95

* Hypoxia * Pulmonary infiltrates on CXR * Fever * Hypotension

Answer 96

* Stop the transfusion * 100% Oxygen * Treat as ARDS * Ventilate as required

Answer 97

* Features: hypotension, dyspnoea, wheezing, stridor, angioedema, bronchospasm, abdominal pain * Mx: stop the transfusion, IM adrenaline, ABC support- O2, fluids * Antihistamine, corticosteroids, bronchodilators may be considered later on

Answer 98

* Give chlorphenamine 10mg slowly IV * Restart transfusion at slower rate and observe more frequently

Haematology including malignancy + blood transfusion Flashcards

(122 cards)