Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

HY Cancer Care > Haematology including malignancy + blood transfusion > Flashcards

Haematology including malignancy + blood transfusion Flashcards

1
Q

Describe the composition of blood?

A

55% plasma:

  • Water
  • Glucose
  • Fat
  • Proteins (hormones, immunoglobulins)
  • Salts/ electrolytes (eg Na, K)
  • Clotting factors

45% haematocrit:
-RBC (erythrocytes)

<1%

  • WBC (leucocytes)
  • Platelets (thrombocytes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where is blood produced & what is the process referred to as?

A
  • Haemopoiesis
  • The production of blood cells begins in utero in the embryonic yolk sac around 14-19days
  • Liver & spleen: from 6 weeks until month 6-7 of fetal life
  • Bone marrow then takes over
  • During childhood there is progressive fatty replacement of marrow in the long bones so that in adult life haemopoietic marrow is confined to the central skeleton- pelvis, vertebrae, ribs, sternum, and proximal ends of long bones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is haematopoiesis?

A
  • The process by which the cellular components of blood are formed
  • multipotent hematopoietic stem cells (HSCs)
    • Myeloid progenitor
      • Megakaryocyte- platelets
      • Erythroblast - reticulocyte - erythrocyte
      • Myeloblast - monocyte + granulocytes = neutrophil/ basophil/ eosinophil
    • Lymphoid progenitor
      • B-lymphocyte - plasma cell
      • T-lymphocyte
      • NK cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name some growth factors which drive the following processes, and where they are made/ released from?

  1. Erythropoiesis
  2. Thrombopoiesis
A
  1. Erythropoietin
    1. 90% produced in kidney peritubular interstitial cells
    2. 10% in liver + elsewhere
    3. No preformed stores
    4. Stimulus to EPO production is the O2 tension in the tissues of the kidne- hypoxia essentially stimulates EPO to be produced, hence EPO production increases in anaemia
    5. EPO stimulates erythropoiesis by increasing the number of progenitor cells committed to erythropoiesis
  2. Thrombopoietin
    1. Produced in liver & kidneys
    2. Increases the number & rate of maturation of megakaryocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What cells are affected in ALL?

A
  • Acute lymphoblastic leukaemia arieses from a clone of lymhpoid progenitor cells
  • Mostly B cells = B-ALL
    • Sub-types such as: t(9;22), t(12;21)
  • Can be T cell = T-ALL
    • Typical presentation- adolescent males with lymphadenopathy or mediastinal mass
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What’s the difference between leukaemia and lymphoma?

A

Leukaemia- affects mainly bone marrow, +/- circulating tumour cells in the blood

Lymphoma- in lymph nodes and solid organs eg spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does acute lymphoblastic leukaemia present?

A

Marrow failure leading to

  • Anaemia- fatigue, breathlessness, angina
  • Neutropenia- infections
  • Thrombocytopenia- petechiae, nose bleeds, bruising

Tissue infiltration leading to

lymphadenopathy, hepatosplenomegaly, bone pain, mediastinal mass (à SVCO), Testicular swelling

Leucostasis leading to altered mental state, headache, breathlessness, visual changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe some genetic risk factors associated with ALL?

A
  • T(12;21)
  • T(9;22)- Philadelphia chromosome (frequency increases with age and offers poor prognosis)
  • T(4;11)- common in infants <12months
  • Down syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How to investigate ALL?

Gold standard diagnosis?

A

Bloods

  • FBC, Renal function, LFTs
    • Normochromic normocytic anaemia + thrombocytopenia
  • Clotting screen
  • Bone profile & Mg
  • Uric acid
  • LDH
  • Viral screen

Blood film

  • Variable number of blast cells

Bone marrow aspiration & biopsy gives definitive diagnosis

  • BM is hypercellular with > 20% leukaemic blasts

Imaging

  • CXR- mediastinal mass
  • CT CAP- assess lymphadenopathy + organ involvement
  • CT/ MRI head- if CNS involvement

Other

  • Pleural tap if PE
  • LP if CNS involvement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Suggest some factors that indicate poorer prognosis in ALL patients?

A
  • Age (worse with advancing age)
  • Performance status > 1
  • White cell count (> 30 for B-cell ALL, > 100 for T-cell ALL)
  • Cytogenetics
  • t(9;22) - Philadelphia chromosome
  • t(4;11)
  • Immunophenotype (pro-B/early and mature-T)
  • CNS involvement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Differentials for ALL?

A
  • Aplastic anaemia
  • Marrow infiltration by other malignancy eg rhabdomyosarcoma, Ewing’s sarcoma
  • AML
  • Infections such as IM or pertussis
  • Juvenile RA
  • ITP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is ALL treated?

A

Chemotherapy- enter pts into national trials

  • Pre-phase therapy: steroids, allopurinol, IV fluids- to ↓ TLS risk
  • Induction chemo: to kill most of the tumour cells + get the pt into remission (= <5 % blasts in BM, normal peripheral blood count + no S/S of disease)
    • Dex, vincristine, asparaginase commonly used
  • Consolidation therapy: intensification blocks to ensure all cells are killed- very intense for pts
    • Vincristine, cyclophosphamide are examples used
  • Maintenance therapy: to reduce recurrence
    • Mercaptopurine daily + weekly methotrexate

Allogenic stem cell transplant- younger pts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Complications of ALL?

A
  • Tumour lysis syndrome
    • After therapy
    • Should be anticipated + given prophylaxis with close monitoring
  • Neutropenic sepsis
  • SVCO
    • Secondary to mediastinal mass
  • Chemo side-effects
    • Early- mucositis, N&V, hair loss
    • Late- cardiomyopathy, secondary malignancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is chronic lymphocytic leukaemia?

A
  • Increased number of mature lymphocytes
    • 98% B-CLL
    • 2% T-CLL
  • This leads to widespread lymphadenopathy and secondary complications such as immune deficiency and cytopaenias
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What age group is affected by CLL?

A
  • Age 60-80
  • Average age of diagnosis is 72; this is a disease of the elderly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

List some cytogenetic factors for CLL?

A
  • Trisomy 12 (extra 12th chromosome)
  • TP53 mutation- major tumour suppressor gene- poor response to treatment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the hallmark feature of CLL?

How does CLL present?

A
  • Hallmark feature is lymphadenopathy due to infiltration of malignant B lymphocytes
  • Often patients are asymptomatic + have the CLL picked up on routine blood tests
  • Painless, enlarged lymph nodes may be present
  • Features of anaemia may be present
  • Thrombocytopenia- bruising or purpura
  • Splenomegaly + less commonly hepatomegaly at later stages
  • Hypogammaglobinaemia causing recurrent infections- early disease bacterial infections & later on, viral and fungal infections such as herpes zoster are seen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are B symptoms?

A
  • Fever
  • Weight loss
  • Drenching night sweats

Classically associated with lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is a diagnosis of chronic lymphocytic leukaemia made?

A
  • Lymphocytosis: excess lymphocytes on FBC (>5x10^9/L) found to be clonal (all same type)- clonality assessed by flow cytometry
  • Blood film- smear or smudge cells- damaged lymphocytes occur during preparation. Also between 70 and 99% of white cells in the film appear as small lymphocytes
  • Normocytic normochromic anaemia in later stages- as a result of marrow infiltration or hypersplenism
    • Autoimmune haemolysis may also occur
  • Thrombocytopenia
  • BM aspiration- lymphocytic replacement of normal BM elements
    • Trephine biopsy reveals nodular, diffuse or interstitial involvement by lymphocytes
  • Reduced concentrations of seurum Ig
  • All of the following autoimmune effects could be seen:
    • Autoimmune haemolytic anaemia
    • Immune thrombocytopenia
    • Neutropenia
    • Red cell aplasia
  • Imaging usually not required- may use USS for hepatosplenomegaly, CXR to exclude alternative diagnosis/ assess for pulm lymphadenopathy or infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is CLL staged?

A

Binet staging

  1. < 3 lymphoid sites (avg survival 10 years +)
  2. =/>3 lymphoid sites (avg survival 8 years +)
  3. Presence of anaemia +/- thrombocytopenia (avg survival 6.5 years +)

Rai staging

  • Stage 0: lymphocytosis
  • Stage I: lymphocytosis + lymphadenopathy
  • Stage II: lymphocytosis + enlarged liver/ spleen +/- lymphadenopathy
  • Stage III: lymphocytosis + anaemia +/- lymphadenopathy +/- organomegaly
  • Stage IV: lymphocytosis + thrombocytopenia +/- lymphadenopathy +/- organomegaly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How is CLL managed?

A

Cure is rare- approach is conservative: aim for symptom control rather than normal blood counts

  • Watch & wait- every 3 months monitor FBC and assess lymphadenopathy, organomegaly

Chemotherapy- many pts never need chemo as chemo can shorten lifespan. Treatment is given for troublesome organomegaly, haemolytic episodes, BM suppression – Binet stage C or sometimes B

  • Tyrosine kinase inhibitors eg imatinib- long remissions & normal life expectancy
  • Corticosteroids may be used as a single agent in very frail pts or to treat AIHA and immune thrombocytopenia

If chemo fails- allogenic stem cell transplant may be an option (donor stem cells following chemo)

Supportive care

  • Vaccination: influenza, pneumococcal (ensure no contraindication with current therapy)
  • Antibiotics for infections
  • Consider intravenous immunoglobulin: treatment of secondary hypogammaglobulinaemia (i.e. IgG < 5g/L)
  • Consider Pneumocystis jirovecii pneumonia (PJP) and herpes zoster prophylaxis: usually in patients on treatment for relapsed CLL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Complications of CLL?

A
  • Richter transformation (3-7%)- formation of aggressive lymphoma, rapid deterioration, poor prognosis
  • Hodgkin lymphoma
  • Multiple myeloma
  • Infections- herpes zoster
  • Autoimmune- AIHA
  • Hyperviscosity syndrome
  • AML
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does presence of BCR-ABL1 mean?

A

Diagnosis of CML and a form of ALL- specifically B-ALL

Very rarely can be linked to AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is aplastic anaemia and what is pancytopenia?

Differential diagnosis for pancytopenia?

A

Pancytopenia means that all of the cell lines (white cells, red cells, and platelets) are decreased in the blood: either the marrow isn’t making enough cells, or it’s so full of other stuff eg fibrosis + has no room to make new cells. Sometimes can be seen in splenomegaly too

  • B12 deficiency
  • Drugs eg methotrexacte, abx
  • Viral infection could suppress BM
  • Leukaemia

If you have a pt with pancytopenia, you have to do a BM biopsy to see if it’s due to an aplastic anaemia

Aplastic anaemia: a distinct, definable disease, where the bone marrow fails to produce blood cells, the bloods show a pancytopenia- defieicny of all blood cell types- RBC, WC, platelets

  • Aplastic anemia can be caused by exposure to certain chemicals, drugs, radiation, infection, immune disease; in about half the cases, a definitive cause is unknown
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What age group is commonly affected by AML?

A

median age of onset is 70

increasingly common with age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Some non-congenital risk factors for AML?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Congenital risk factors for AML?

A
  • Down syndrome
  • Congenital neutropenia
  • Fanconi anaemia- rare genetic disorder, inherited BM failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Clinical features of AML + reason for them?

A

Marrow failure leading to anaemia, neutropenia, thrombocytopenia

Tissue infiltration leading to lymphadenopathy, hepatosplenomegaly, bone pain, gum hypertrophy, skin deposits, testicular enlargement

Leucostasis leading to altered mental status, headache, dyspnoea, visual changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How is a diagnosis of AML made?

Describe some labaratory findings in AML patients? + other investigations to do?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Management of AML:

  1. What is the immediate supportive management?
  2. What is the definitive management? How is care co-ordinated throughout the country?
  3. Complications?
A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Adverse prognostic factors for AML?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the hallmark genetic finding in CML?

A

Philadelphia chromosome (22)

causes abnormally activated tyrosine kinase: BCR-ABL1 protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Signs & symptoms of CML?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe some labaratory findings in CML

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How is CML treated?

A

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 2nd gen TKI +/- intensive chemo, +/- allo-SCT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Prognosis for CML?

A

Diagnosis age 15-64: 90% 5 year survival

Age 65+: 40% 5 year survival

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the 6th most common cancer in the UK?

A

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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Describe the types of Hodgkin lymphoma?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What cells are seen in Hodgkin lymphoma?

A

Hodgkin/ Reed-Sternberg cells (HRS cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Who gets Hodgkin lymphoma?

A
  • Any age
  • Rare in ch. + peak incidence in young adults
  • 2:1 male
  • EBV
  • Smoking
  • HIV
  • Immunosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Describe some clinical features of patients with Hodgkin lymphoma?

A
  • 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

How is Hodgkin lymphoma diagnosed? Name 1 single investigation

A

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

  • immunophenotyping of HRS cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What blood tests would you request for suspected Hodgkin lymphoma and what would you expect to see?

What imaging is required?

Any other investigations you can think of?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Describe the clinical staging system for Hodgkin lymphoma?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

How is Hodgkin lymphoma treated?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Why must Hodgkin lymphoma pts receive irradiated blood?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Prognosis of Hodgkin lymphoma?

A
  • Limited disease: stage I and II- 90% survive 5 years
  • Advanced disease: III and IV- 75-90% survive 5 years
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Suggest some long term complications of having Hodgkin lymphoma (and treatment)

A
  • Developing cancer secondary to radiotherapy- lung and breast cancer
  • Intestinal complications
  • Sterility/ infertility
  • Mediastinal radiation effectsà coronary artery disease or pulmonary disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is non-Hodgkin lymphoma?

A

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
50
Q

Describe some infectious causes of non-hodgkin lymphoma

A
  • EBV: Burkitt lymphoma
  • HIV: high grade B cell lymphoma
  • Hep C: marginal zone lymphoma
  • H pylori: gastric lymphoma (MALT)
  • Malaria: Burkitt lymphoma
51
Q

How do patients with NHL present?

A

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
52
Q

How is NHL investigated?

A

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
53
Q

Most common chemotherapy regimen for Non-Hodgkin lymphoma?

A

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
54
Q

Types of non-Hodgkin lymphomas?

A

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
  • 2nd 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
55
Q

Differentials for lymphocytosis?

A

= high white cell count

Infections

  • CMV
  • Hep B, C
  • TB

ALL or CLL

Hypothyroidism

56
Q

What investigation can be performed to determine if lymphocytosis is reactive (polyclonal) or clonal?

A

Flow cytometry- shows markers on cells

57
Q

What are the short and long term risks associated with splenectomy?

A

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
58
Q

A 48 yr old man is referred by his GP to haematology clinic with an enlarged lymph node on the left side of his neck.

What questions will you ask?

What is your differential diagnosis?

What clinical features will you specifically look for on examination?

A
  • 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
59
Q

What’s the difference between a core biopsy and an excisional biopsy?

A

Excision biopsy- taking it all out- this is best

Core biopsy- takes a part- good if things are inaccessible but get much less tissue

60
Q

What considerations are needed before starting hydroxycarbamide? What is this drug used for?

A

Uses-

  • Polycythaemia vera
  • Essential thrombocythaemia
  • Chronic myeloid leukaemia

Consderations-

  • Teratogenic effects
  • Myelosuppression
  • Kidney and liver function
61
Q

Differentials of lymphadenopathy?

A
  • Mets of primary solid malignancy
  • Infections
  • Autoimmune disease eg SLE, RA
  • Graft versus host disease
  • Sarcoidosis
  • Drugs eg phenytoin, isoniazid, allopurinol
  • Covid vaccine
62
Q

Side effects/ complications of chemotherapy?

A
  • Fatigue
  • N&V
  • Diarrhoea and constipation
  • Hair loss
  • Infections
  • Anaemia
  • Bruising and bleeding
  • Mucositis
  • Loss of appetite
  • Skin and nail changes
  • Insomnia
  • NEUTROPENIC SEPSIS
63
Q

What is multiple myeloma?

A

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
64
Q

Difference between innate and adaptive immunity?

A

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
65
Q

Describe the pathophysiology of myeloma?

A
  • 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
66
Q

What is a mnemonic for multiple myeloma?

A

SLiM CRAB

  • Sixty % plasmacytosis
  • Light chains I/U > 100
  • MRI 1 or more focal lesion
  • Calcium elevation
  • Renal insufficiency
  • Anaemia
  • Bone disease
67
Q

Why do myeloma patients develop renal failure?

A

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
68
Q

Outline the very basic pathological and clinical features of primary amyloidosis

A
  • 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
69
Q

Distinguish between multiple myeloma, MGUS and benign polyclonal hypergammaglobinaemia

Also- what is smouldering myeloma?

A

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
70
Q

What is MGUS?

How many go on to develop myeloma?

A

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
71
Q

Describe the clinical features of myeloma & why they occur?

A
  • 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
72
Q

Describe some symptoms a patient with myeloma could present with?

A
  • 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)
73
Q

Multiple myeloma can be asymptomatic. It can present with abnormalities on blood tests, name a few?

A
  • Normochromic, normocytic anaemia
  • Renal impairment
  • Hypercalcaemia
  • Raised erythrocyte sedimentation rate (ESR), plasma viscosity, serum protein, or globulin
74
Q

How can Bence Jones proteins cause anaemia in myeloma patients?

A
  • 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
75
Q

What should you do if you suspect myeloma? Include blood tests & imaging

A

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
76
Q

How is myeloma screened for?

A

‘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
77
Q

Diagnostic criteria for multiple myeloma?

A
  • 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

78
Q

What are the risk factors for myeloma?

A
  • Age
  • Male
  • Black African ethnicity
  • FHx
  • Obesity
79
Q

Describe the principles of treating myeloma

A
  • 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
80
Q

What are some complications of myeloma?

A
  • 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
81
Q

How is myeloma bone disease managed?

A
  • 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
82
Q

Prognosis for myeloma?

A
  • 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).
83
Q

Outline the functions of the spleen

A

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
84
Q

Discuss the mechanisms and causes of splenomegaly

A
  • 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
85
Q

List the important causes & management of hyposplenism.

What does a blood film show in someone with hyposplenism?

A

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
86
Q

What is the most common age group for Non-Hodgkin lymphoma?

A
  • 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
87
Q

How are NHL’s classified?

A
  • 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)

88
Q

How do pts with diffuse large B cell lymphoma present?

A
  • 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
89
Q

How do pts with follicular lymphoma present?

A
  • B cell NHL, second most common form of NHL
  • Often presents insidiously, gradual lymphadenopathy (painless)
  • B symptoms
90
Q

How does Burkitt’s lymphoma present? Also who is commonly affected?

A
  • 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
91
Q

Define thrombocytopenia?

A
  • 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
92
Q

What are some common causes of thrombocytopenia?

A
  • 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
93
Q

Describe the presenting symptoms, signs and blood count abnormalities of autoimmune (idiopathic) thrombocytopenic purpura (ITP)

A
  • 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
94
Q

Describe the presenting symptoms, signs and blood test abnormalities of thrombotic thrombocytopenic purpure (TTP)

A
  • 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
95
Q

Management of TTP?

A
  • Plasma exchange
  • Steroids
  • Rituximab
96
Q

Describe The ABO blood group system?

A
  • 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
97
Q

Describe the Rh D antigens and antibodies? How is haemolysis in newborn prevented?

A
  • 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
98
Q

Explain the significance of allo-antibodies in relation to blood transfusion and haemolytic disease of the new-born

A
  • 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
99
Q

Causes of jaundice in the first 24 hours of life?

A
  • Rhesus haemolytic disease
  • ABO haemolytic disease
  • Hereditary spherocytosis
  • Glucose-6-phosphodehydrogenase
100
Q

Explain what is meant by Group and Screen, Crossmatch (compatibility tests), and electronic issue

A
  • 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
101
Q

Describe the indications for red cell transfusion

A
  • 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
102
Q

Discuss the indications for platelet transfusion

A
  • 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
103
Q

Discuss the indications for the use of fresh frozen plasma (FFP), cryoprecipitate and prothrombin complex concentrate

A
  • 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
104
Q

What to do when pts taking warfarin require immediate or urgent surgery?

A
  • 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
105
Q

Indications for irradiated blood?

A
  • Blood transfusion from 1st/2nd degree relatives
  • Congenital immunodeficiency states
  • Autologous/ allogenic haematopoietic progenitor cell transplant (BM or peripheral)
  • Hodgkin’s disease (lifelong)
  • Specified in particular treatment protocol
106
Q

Indications for CMV negative blood components?

A
  • 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)
107
Q

Define major haemorrhage

A
  • 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
108
Q

Describe the management of massive blood loss

A
  • 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
109
Q

Suggest some scenarios where major haemorrhage can be declared?

A
  • 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
110
Q

What are some alternatives to blood transfusion and discuss the need to conserve the blood supply?

A
  • For pts before surgery-
    • IV/ oral iron
    • Cell salvage
    • Tranexamic acid (anti-fibrinolytic)
111
Q

List some potential risks of blood transfusion

A
  • Reactions
    • Acute haemolytic reaction/ ABO incompatibility
    • TRALI
    • Fluid overload
    • Anaphylaxis
    • Allergy- urticaria, itch
  • Infections
    • Viral- HIV, hep B, hep C, CJD
    • Bacteria- contamination
112
Q

List some complications of blood transfusion

A
  • 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
113
Q

What are some signs/ symptoms of giving a pt the wrong unit of blood?

A
  • 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
114
Q

How is ABO mismatch treated?

A
  • 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
115
Q

Complications of acute haemolytic transfusion reaction?

A
  • Disseminated intravascular coagulation
  • Renal failure
116
Q

How to manage a non-haemolytic febrile reaction during or after a blood transfusion?

A
  • 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
117
Q

Features of TACO?

A
  • Pulmonary oedema
  • Hypertension
118
Q

How is TACO treated?

A
  • Slow or stop transfusion
  • Consider IV loop diuretics - furosemide 40-80mg IV and O2
119
Q

Features of TRALI?

A
  • Hypoxia
  • Pulmonary infiltrates on CXR
  • Fever
  • Hypotension
120
Q

How is TRALI treated?

A
  • Stop the transfusion
  • 100% Oxygen
  • Treat as ARDS
  • Ventilate as required
121
Q

Features & management of anaphylaxis during blood transfusion?

A
  • 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
122
Q

How to manage a mild allergic reaction during a blood transfusion?

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

HY Cancer Care (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions