Haematology 2 Flashcards
1
Q
What are the two types of thrombosis?
A
Arterial - e.g. MI or stroke (high pressure system where thrombi is platelet rich so treat with anti-platelets (aspirin or clopidogrel)
Venous - e.g. DVT or PE (low pressure system where thrombi is fibrin rich - treat with anticoagulants to suppress coagulation cascade e.g. heparin or DOACs
2
Q
what are some risk factors for arterial thrombosis?
A
- smoking
- obesity
- hypertension
- DM
- older age
- there are no inherited arterial thrombophilias
3
Q
what are some risk factors for venous thrombosis?
A
Acquired: age, previous VTE, surgery/trauma, immobility, obesity, cancer, pregnancy, serious illness, contraceptive pill, HRT, immobility, long haul flights, polycythaemia, SLE
Inherited: thrombophilia e.g. Factor V leiden (most common), protein C or S deficiency, antithrombin deficiency, anti-phospholipid syndrome
4
Q
what is a DVT?
A
it is a clot in the veins
can occur in any vein - but usually in major deep veins of pelvis and legs
* if they occur in other locations e.g. arm they are often idicative of a more sinister underlying cause (e.g. clotting disorder, carcinoma)
they can embolise and travel through the right side of the heart and into the lungs where it becomes lodged in the pulmonary arteries and causes a pulmonary embolism
5
Q
why does a venous thromboembolism usually occur?
A
they usually occur secondary to stagnation of blood and hyper-coagulable states.
6
Q
what is given as VTE prophylaxis to patients admitted to hospital?
A
if they are at increased risk of VTE they should recieve LMWH (enoxaparin). If contraindicated - warfarin or a DOAC.
Anti-embolic compression stocking are also used (unless contraindicated - in things such as significant peripheral arterial disease.
7
Q
how would a DVT present?
A
- almost always unilateral
- calf or leg swelling
- tenderness of the calf
- superficial veins
- pitting oedema
- redness
8
Q
what is Virchow’s triad?
A
the three main causatory factors that lead to DVT
- stasis
- hypercoaguability
- vessel wall injury
9
Q
what investigations would you use for DVT?
A
- first of all you would perform a wells score
- D-dimer is sensitive but not specific (other conditions such as pneumonia, malignancy, heart failure, surgery, pregnancy can cause a raised d-dimer)
- USS doppler of the leg
10
Q
what is included in a well score ?
A
active cancer (1 point) calf swelling (at least 3cm larger than other side)(1 point) prominent superficial veins (1 point) pitting oedema (1 point) swelling of entire leg (1 point) localised pain along distribution of deep vein system (1 point) paralysis or paresis or recent cast immobilisation of lower extremities (1 point) Recent bed rest >3 days or major surgery in past 12 weeks (1 point) previous history of DVT (1 point) alternative diagnosis just as likely (2 points)
DVT likely: 2 points or more
DVT unlikely: 1 point or less
11
Q
what actions should you take following a Wells score?
A
If DVT is likely (2 points or more):
> a proximal leg vein USS should be carried out within 4 hours: if positive then the diagnosis of DVT is made and anticoagulation treatment should start. If result is negative do a d-dimer to confirm negative result
> if the USS can not be carried out within 4 hours a D-dimer test should be performed and interim therapeutic anticoagulation (a DOAC) administered whilst waiting for USS (which should be performed within 24 hours)
> if scan is negative but D-dimer is positive - stop interim anticoagulation but offer proximal leg vein USS 6 to 8 days later
if DVT is unlikely (1 point or less)
> perform a D-dimer test (should be done within 4 hours, if not, give an interim anticoagulation
>if test is -ve then DVT unlikley
> if +ve then do proximal vein USS
12
Q
how is DVT managed?
A
The first line is apixaban or rivaroxaban (both DOACs) - offered first line following confirmation of DVT (new guidelines) - in non pregnant
If starting warfarin, must have two consecutive INR readings >2.0 before stopping LMWH (termed bridging therapy)
Continue anticoagulation for:
3 months: if there is an obvious reversible cause
Beyond 3 months if the cause is unclear, there is recurrent VTE or there is an irreversible underlying cause such as thrombophilia.
6 months - in active cancer then review.
beyond 6 months - recurrent DVT
13
Q
what are the different coagulation tests?
A
Prothrombin time (PT) - it is prolonged by coumarins (warfarin), VK deficiency and liver disease.
Activated partial thromboplastin time (APTT) - increased in heparin treatment, haemophilia, antiphospholipid syndrome or DIC
INR - ratio of the time the time the samples takes to clot compared to the control
14
Q
what clotting factors does heparin affect?
A
prevents activation factors 2,9,10,11
15
Q
what clotting factors does warfarin affect?
A
affects synthesis of factors 2,7,9,10
16
Q
what can cause thrombocytopenia?
A
reduced platelets
decreased production: congenital (malfunctioning bone barrow)
bone marrow infiltration (leukaemia, metastasis, lymphoma, myeloma, myelofibrosis),
Impaired platelet production (low B12/folate, reduced thrombopoietin (liver disease), medication e.g. methotrexate or chemo, alchohol, HIV, TB, autoimmune aplastic anaemia
Increased destruction - ITP, hypersplenism, heparin induced thrombocytopenia, DIC, thrombotic thrombocytopenia purpura.
17
Q
what is myelodysplastic syndrome?
A
aka myelodysplasia
it is a group of clonal stem cell disorder characterised by ineffective and dysplastic haematopoiesis resulting in one or more cytopenias and a varying prediction to develop AML.
It is believed that environmental exposures, hereditary factors and gene alterations and deletions contribute to the development of a neoplastic multi-potential haematopoietic stem cell clone.
18
Q
what are the diagnostic features of myelodysplasia syndrome?
A
It causes low levels of blood components that originate from the myeloid cell line: anaemia, neutropenia, thrombocytopenia
common in older age >70years
often asymptomatic - usually only found on lab findings
Anaemia: Fatigue, exercise intolerance, pallor, purpura, petechiae
19
Q
how is myelodysplastic syndrome diagnosed?
A
FBC - one or more cytopenias
reticulocyte count will be inappropriately normal or low
Rule out folate and B12 and iron deficiency as cause of anaemia
Rule out HIV as a cause of any of the cytopenias
Bone marrow aspiration with iron stain - single of multilineage dysplasia (bone marrow blasts <20%)
Bone marrow biopsy - hypercellular marrow
20
Q
how is myelodysplastic syndrome managed?
A
if asymptomatic - monitor
> haematopoietic growth factors - epoetin alpha
blood transfusion (RBC or Platelet transfusions)
if severe - chemotherapy - azacitidine
Stem cell transplant
21
Q
what is ITP?
A
immune thrombocytopenic purpura: is an autoimmune haematological disorder characterised by isolated thrombocytopenia in the absence of an identifiable cause.
22
Q
what are the two types of ITP?
A
Primary (acute): isolated thrombocytopenia with no identifiable cause. The thrombocytopenia is secondary to an autoimmune phenomenon and involves antibody destruction of peripheral platelets. Most commonly in children aged 2-6 years. May follow recent viral infection or immunisations. It is self limiting purpura over 1-2 weeks. There will be acute onset of muco-cutaneous bleeding)
Secondary (chronic) - includes all forms of ITP where associated medical conditions or precipitants can be identified. more common in woman, associated with other autoimmune disorders e.g. SLE, thyroid disease, autoimmune haemolytic anaemia, also seen in patients with CLL and solid tumours. Platelet autoantibodies
23
Q
how does ITP present?
A
> common in age <10 or >65
- bleeding (signs of bleeding - bruising, petechiae, haemorrhagic bullae, bleeding gums)
- absence of systemic symptoms
24
Q
how is ITP diagnosed?
A
FBC - thrombocytopenia
platelet autoantibodies seen in 60-70% of patients
25
how is ITP managed?
In children - will usually resolve spontaneously
IVIG plus prednisolone plus platelet transfusions
if this doesn't work - mycophenolate or rituximab
26
what is heparin induced thrombocytopenia?
it is a severe drug reaction to heparin that can lead to life and limb threatening venous and/or arterial thromboembolism.
There is development of IgG antibodies against Heparin-platelet activation and consumption which results in thrombocytopenia. Platelt activation results in severe thrombosis (arterial or venous) and skin necrosis.
This results in thrombocytopenia and/or thrombosis
Typically it develops 5-10 days after exposure
27
how does heparin induced thrombocytopenia present?
necrosis at heparin injection sites
| features consistent with recent venous or arterial thromboembolic event (e.g. PR,DVT, stoke, MI)
28
how is heparin induced thrombocytopenia managed?
stop heparin immediately and administer VK
| add a non heparin alternative - e.g. fondaparinux or a direct acting oral anticoagulant
29
what is TTP?
Thrombotic thrombocytopenic purpura
It is a clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura.
Without treatment it is typically fatal
30
what is the pathogenesis of TTP?
the underlying cause may involve the production of unusually large amounts of vWF multimers.
These multimers build up due to lack of ADAMTS-13 which is a protease responsible fo vWF degradation.
The lack of ADAMTS-13 is though to be secondary to an autoimmune process or a genetic mutation
The large amount of vWF with platelet membranes - this interaction triggers aggregation of circulating platelets at the sites of high intravascular stress which results in thrombi in the microvasculature system.
The blood clots in the small vessels break up RBCs leading to a haemolytic anaemia
31
how does TTP present?
There may be a non-specific prodrome
Severe neurological symptoms - coma, focal abnormalities, seizure
Digestive symptoms secondary to microthrombi in the bowel - nausea, vomiting, diarrhoea, abdominal pain
32
what investigations would you perform for TTP?
Platelet count - decreased
Hb - usually decreased
Peripheral smear - microangiopathic blood film with schistocytes
Reticulocyte count is typically raised in TTP
Urinalysis may show proteinuria
Direct Coombs test to rule out autoimmune haemolytic anaemia
33
how would you treat TTP?
> plasma exchange - to remove ADAMTS-13 antibody and provide ADAMTS-13 source
> Corticosteroids - oral prednisolone or IV methylprednisolone
> Monoclonal antibody - caplacizumab
34
what is DIC?
disseminated intravascular coagulation
it is an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors
35
what are the causes of disseminated intravascular coagulation?
- sepsis/severe infection, major trauma or burns
- some malignancies - AML or metastatic mucin-secreting adenocarcinoma
- obstetric disorders - amniotic fluid embolisation, eclampsia, abruptio placentae, retained dead fetus syndrome
- severe organ destruction of failure - severe pancreatitis or acute hepatic failure
- vascular disorders - kasabach-merritt syndrome or giant haemangiomas, large aortic aneurysms
36
what are the diagnostic features of DIC?
- presence of underlying disorder
- oliguria, hypotension or tachycardia
- purpura fulminans, gangrene, acral cyanosis (systemic sigs of microvascular/macrovascular thrombosis)
- patient will be actively ill an shocked
- bleeding from mouth, nose and venepuncture sites
- widespread bruising and purpura
- vessel occlusions
- delerium and come
37
what investigation would you order for DIC?
```
FBC - platelet count decreased (severe thrombocytopenia)
Prothrombin time - often prolonged
APTT - unpredictable
Fibrinogen - decreased
D-dimer - raised
```
38
how do you manage DIC?
- treat underlying cause
- platelet transfusion and fresh frozen plasma to replace coagulation factors and coagulation inhibitors
- cryoprecipitate to replace fibrinogen and some coagulation factors
- RBC transfusions in those who bleeding profusely.
39
what is haemophilia?
Haemophilia is a X-linked recessive disorder of coagulation.
It is due a deficiency in coagulation factor.
Haemophilia A result from deficiency of clotting factor VIII (8).
Haemophilia B results from the deficiency of clotting factor IX (9).
*X-linked recessive inheritance - man with haemophilia -> all daughter are carriers and all sons have disease.
Mother carrier and unaffected father - half daughters carriers and half sons disease.
40
What are the diagnostic factors for haemophilia?
- presence of risk factors (family history, male sex, for acquired haemophilia - age >60 and autoimmune disorders.
- history of recurrent or severe bleeding
- bleeding into muscles - presents with pain and swelling of the involved area
- the hallmark of severe disease is recurrent spontaneous bleeding into joints and muscle which can lead to crippling arthritis if not treated.
- also bleeding from gums, Gi tract, urinary tract, retroperitoneal space, intracranial
- 40% of patients will present in the neonatal period with intracranial haemorrhage or prolonged oozing from the heel prick and venepuncture sites
41
how is haemophilia investigated?
aPTT will be prolonged
plasma factor VIII or IX are used to establish diagnosis and severity
prothrombin time will be normal
42
how is haemophilia managed?
Recombinant factor VIII for haemophilia A and recombinant factor IX concentrate for haemophilia B - given by IV infusion whenever there is bleeding
Prophylactic factor VIII is given to all children from the age of 2 years to reduce risk of chronic joint damage
for mild haemophilia A - desmopressin can be used (it stimulates endogenous release of factor VIII and vWF)
43
what is thrombophilia?
it is a hypercoaguable state - it leads to increased risk of venous thrombosis due to an abnormality in the coagulation system.
It may be inherited or acquired
44
what are the causes of thrombophilia?
Group 1 and 2: inherited causes
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
- plasminogen deficiency
- dysfibrinogenaemia
- factor V Leiden
- Prothrombin gene mutation
- sickle cell disease
Group 3 - mixed or unknown aetiology
- increased fibrinogen levels
- increased levels of coagulation factor VIII
- increased levels of coagulation factor IX or XI
- hyperhomocystenaemia
Acquired causes:
- risk factors for hypercoaguable state - e.g. obesity and smoking
- pregnancy/postpartum
- malignancy
- acute inflammatory state
- myeloproliferative disorders
- nephrotic syndrome
- HIV
- DIC
- proximal nocturnal haemoglobuninuria
- heparin induced thrombocytopenia
- COCP
- chemo
- surgery
- long haul flights
45
what is Von Willerbrand disease?
It is the most common inherited cause of abnormal bleeding (haemophilia)
There are many underlying genetic causes - most of which are AD.
There is either, deficiency, absence or malfunctioning Von willerbrand factor.
46
what is the role of vWF?
it is a glycoprotein with promotoes platelet adhesion to damaged endothelium - it is a carrier molecule for factor VIII
47
what are the different types of vWD?
type 1 - partial reduction in vWF (80% of patients)
types 2 - abnormal form of vWF
> 2a - lack of high molecular weight vWF
>2b - defective adhesion due to increased binding
>2m - decreased platelet dependent vWF function
>2n - failure to bind to factor VIII
type 3 - total lack of vWF (autosomal recessive - the most severe form)
48
how will vWD present?
- bleeding from minor wounds
- post operative bleeding
- family history of bleeding
- easy and excessive bruising
- menorrhagia
- gastrointestinal bleeding
- epistaxis
49
what investigations would you perform for vWD?
prothrombin time will be within the reference range - as this is a measure of the extrinsic pathway
activated partial prothrombin time - may be prolonged but only if factor VIII is less the 35% of normal levels
(a normal APTT does not rule out VWD)
FBC - will be normal apart from in type 2B when the platelet count may be reduced
quantitative immunoassay/functional assay of vWF
50
how is VWD managed?
- avoid platelets and antiplatelet drugs
- vWF containing concentrate
- desmopressin can be used as it stimulates the release of VWF
if woman have chronic menorrhagia:
- tranexamic acid
- mefanamic acid
- norethisterone
- COCP
- mirena coil
- hysterectomy may be required in sevre cases.
51
what are the different types of leukaemia?
it is the name of cancer of a particular line of stem cells in the bone marrow - this causes unregulated production of certain types of blood cells.
They are classified on how rapidly they progress (slow=chronic, fast = acute) and the cell line that is affected - myeloid or lymphoid
AML usually over 75's
ALL - usually under 5's but also over 45
CML - over 65's
CLL - over 55's
52
what is the pathophysiology of leukaemia?
a genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell - the excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types. This results in a pancytopenia.
53
how does acute myeloid leukaemia present ?
- usually occurs in older adults
- pallor
- signs of thrombocytopenia - bleeding, bruising, petechiae
- signs of anaemia - fatigue, dizziness, palpitations, dyspnoea
- infections or fever as a reult of leukopaenia
- lymphadenopathy
- hepatosplenomegaly
- bone pain
* generally the prognosis is poor
* it can be the result of a transformation from a myeloproiferative disorder such as polycythaemia vera or myelofibrosis
54
what investigations would you perform for AML?
FBC - despite the elevation in WBC, many patients have severe neutropenia, anaemia, macrocytosis, leukocytosis and thrombocytopenia
Peripheral blood smear - blasts on the blood film, presence of Auer rods
coagulation panel
Bone marrow biopsy - bone marrow hypercellularity and infiltration by blasts, blasts >20%
55
how is AML managed?
- manage with MDT
- chemotherapy
- steroids
- radiotherapy
- bone marrow transplant
56
what chromosome is present in most patients with chronic myeloid leukaemia?
the Philadelphia chromosome is present in more than 95% of patients - it is due to a translocation between the long arm of chromosome 9 and 22.
This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22
The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal and causes abnormal expansion of myeloid cells in the bone marrow and peripheral blood.
57
what are the different phases of CML?
Chronic phase - can last around 5 years, it is often asymptomatic
Accelerated phase - occurs where the abnormal blasts take up a high proportion of the cells in the bone marrow and blood. In this phase patients become more symptomatic, develop anaemia, thrombocytopenia and become immunocompromised
Blast phase - follows the accelerated phase and involves an even higher proportion of blasts cells and blood - this phase has severe symptoms of pancytopenia and is often fatal. - It can cause acute myeloid or acute lymphoblastic leukaemia.
58
how does CML present?
- splenomegaly - occurs in 75% of patients
more likely to get symptoms in the accelerated or blast phase
59
what investigations should you perform for chronic myeloid leukaemia?
FBC - elevated WBC count, they may have anaemia a normal platelet counts, thrombocytosis. if they present in the accelerated or blast phase they may have thrombocytopenia
Peripheral blood smear - almost all WBCs will be mature or maturing myeloid cells, elevated basophils and eosinophils
Bone marrow biopsy will show granulocytic hyperplasia
Cytogenetic studies, FISH and molecular analysis (PCR) to confirm the Philadelphia chromosome
60
how is CML managed?
1st line - a tyrosine kinase inhibitor - e..g. imatinib
If no remission or relapse or disease progressin - allogenic haematopoietic stem cell transplant plus high dose iduction chemo
61
how does acute lymphoblastic leukaemia present?
- lymphadenopathy
- hepatosplenomegaly
- anaemia - pallor and lethargy, dizziness, palpitations
- neutropenia - severe of frequent infections, fever
- thrombocytopenia - easy bruising, petechiae, epistaxis
- if there is CNS infiltration - papilloedema, nuchal rigidity and meningismus
- if the testicles are involved there may be painless unilateral testicular enlargement
- infiltration of the renal cortex by leukaemic blast cells can cause renal enlargement
- bone pain
62
what are the different types of ALL?
common ALL (75%) - CD10 present, pre-B phenotype
T-cel ALL (20%)
B-cell ALL (5%)
63
what are poor prognostic factors for ALL?
```
age < 2years or >10 years
WBC >20*10 to the power of 9 at diagnosis
T or B cell surface markers
non-caucasian
male sex
```
64
what investigations would you perform for ALL?
FBC - Anaemia (normocytic, normochromic with a low reticulocyte count present), leukocytosis, neutropenia and/or thrombocytopenia
Peripheral blood smear - leukaemic lymphoblasts
Serum electrolytes - uric acid elevation reflects the extend of tumour burden, hypercalcaemia may be caused by bony infiltration or ectopic release of a parathyroid hormone, hyperkalaemia may occur as a result of extensive leukaemic cell lysis.
Bone marrow aspiration - bone marrow hypercellularity and infiltration of lymphoblasts
CXR - may show evidence of a mediastinal mass, pleural effusion or lower resp tract infection. Mediastinal widening is common in T lymphoblastic leukaemia.
65
how is ALL managed?
It is fatal within months if left untreated
Blood and platelet transfusions
chemotherapy
tyrosine kinase inhibitor - if they have Philadelphia chromosome
prophylactic antibiotics (ciprofloxacin) as they have severe neutropenia so are at risk of deadly infections
Stem cell transplants can be curative
66
what is CLL?
it results from a progressive accumulation of functionally incompetent B lymphocytes.
The cells fo origin in patients with CLL are clonal B cells arrested in the B-cell differentiation pathway.
67
how doe CLL present?
often no symptoms
wide spread lymphadenopathy that is painless
Marrow failure and immunosuppression - anaemia and frequent infections
Hepatomegaly
splenomegaly
68
what investigations of CLL?
WBC - elevated with absolute lymphocytosis
Blood film - smudge/smear cells present, spherocytes and polychromasia can be seen if there is active haemolysis
Hb - if there is anaemia present this indicates a poor prognosis
platelet count - thrombocytopenia also indicates poor prognosis
Immunophenotyping - done to analyse the surface markers - mainly CD19/20 and CD5+ B cells which may weakly express surface immunoglobulins
Coombs test - may be positive if there haemolysis
Bone marrow aspiration and biopsy is not required in all cases of CLL but may be needed to establish diagnosis
69
what are the staging system for CLL ?
Rai or Binet staging system for CLL - it can help to determine how to treat the patient
70
how is CLL managed?
blood transfusions
chemotherapy - chlorambucil is first line - combine with prednisolone
stem cell transplant
71
what is the progression of CLL?
many patients stay stable for years and may even regress
death is often due to complication of an infection
Autoimmune haemolytic anaemia can occur
```
Richter syndrome - 3-10% of cases - CLL is transformed into an aggressive large B cell lymphoma. EBV may play a role in this transformation - lymph node biopsy is needed for diagnosis
The patient may present with:
- weight loss
- fever
- night sweats
- muscle wasting
- increasing hepatosplenomegaly
- lymphadenopathy
```
72
what is APML?
acute promyelocyte leukaemia
an uncommon variant of AML
it involves specific mutation t(15:17)
there is almost always coagulopathy and this is often the cause of death
73
what is lymphoma?
it is a disorder caused by malignant proliferation of lymphocytes which accumulate in the lymph nodes causing lymphadenopathy but also may be found in the peripheral blood or infiltrate organs.
74
what are the two main types of lymphoma?
Hodgkin's lymphoma
Non-Hodgkin's lymphoma
75
what age group is hodgkins lymphoma common in?
Two peaks :
around 20
around 75
76
what is Hodgkins lymphoma?
it is an uncommon haematological malignancy arising from mature B cells.
The B cells no longer express surface immunoglobulin (IgG) and no longer undergo apoptosis - they become massive large cells that no longer perform their original function.
77
what increases risk of Hodgkin's lymphoma?
Mononucleosis infections: EBV infection and CMV infection
78
how does Hodgkin's lymphoma present?
lymphadenopathy is the key presenting symptom - characteristically non-tender and feel rubbery.
Some patients will experience pain in the lymph nodes when they drink alcohol
B symptoms - fever, weight loss, night sweats
other symptoms include: fatigue, itching, cough, SOB, abdominal pain, recurrent infections
79
what investigations would you perform for Hodgkin's lymphoma?
FBC - if no bone marrow involvement may be normal, if there is bone marrow involvement there may be low Hb and platelet, there may be lymphocytopenia or eosinophila.
ESR - raised
CXR - mediastinal mass
lymph node biopsy - required for definitive diagnosis - presence of reed sternberg cells
serum LDH - if raised = bad prognostic factor
contrast CT
PET-CT
80
how is Hodgkins lymphoma staged?
using the Ann Arbor system
Staging with definition:
I: involvement of a single lymph node region or lymphoid structure (e.g., spleen, Waldeyer ring)
II: involvement of 2 or more lymph node regions on the same side of the diaphragm
III: involvement of lymph node regions or structures on both sides of the diaphragm
IV: involvement of extra-nodal site(s) beyond that designated E.
Annotations:
A: no B symptoms
B: fever, drenching night sweats, weight loss
X: bulky disease (>one third widening of mediastinum at T5 and T6, or >10-cm nodal mass)
E: involvement of a single extra-nodal site, contiguous or proximal to known nodal site
81
How is Hodgkin's Lymphoma managed?
radiotherapy and chemotherapy
```
chemotherapy: ABVD
A- Adriamycin
B- Bleomycin
V- Vinblastine
D- Dacarbazine
```
82
what are side effects of radiotherapy ?
Increased risk of secondary malignancies such as - solid lung, breast, melanoma, stomach, sarcoma and thyroid
Increased risk of ischaemic heart disease, hypothyroidism and lung fibrosis due to radiation field
83
what are the side effects of chemotherapy?
Alopecia is common - hair usually returns after completion
Nausea, Vomiting, neuropathy, infertility
Myelosuppression - low blood counts
84
what is a Hickman line?
it is an IV catheter, mainly used in chemotherapy and sometimes dialysis
They can remain in place for weeks or months
85
what are the different histological classification of hodgkins
Nodular sclerosing - most common types, has a good prgnosis, it is more common in woman and is associated with lacunar cells and usually involves the lymph nodes the mediastinum and neck
Mixed cellularity - around 20% - good prognosis - associated with a large number of Reed-Sternberg cells, associated with B symptoms
Lymphocyte predominant - around 5% - has the best prognosis, more common in men
Lymphocyte depleted - rare - has the worst prognosis , associated with HIV
86
what factors are associated with poor prognosis in Hodgkin's lymphoma?
B symptoms
- weight loss >10% in the last 6 months
- fever >38
- night sweats
```
Age >45
stage IV disease
Hb < 10.5
lymphocyte count <600 or < 8%
male
albumin <40
WCC >15000
```
87
what is Non-Hodgkin's lymphoma?
It is an umbrella term used to describe any lymphoma that does not contain Reed-Sternberg cells e.g. Follicular lymphoma or Burkitt's lymphoma
80% are of B-cell origin
20% are of T-cell origin
88
what viruses and bacteria have been found to be associated with Non-Hodgkin's Lymphome?
Epstein-Barr virus (EBV) with Burkitt's lymphoma[7]
EBV with AIDS-related primary central nervous system lymphoma
EBV with nasal natural killer/T-cell lymphoma
Hepatitis C virus (HCV) with splenic marginal zone lymphoma
HCV with diffuse large B-cell lymphoma
Human T-cell lymphotrophic virus type 1 with T-cell lymphoma
Human herpesvirus 8 with primary effusion/body cavity lymphoma in HIV patients
Helicobacter pylori with gastric mucosa-associated lymphoid tissue (MALT)
Borrelia burgdorferi with MALT lymphoma (cutaneous type)
Coxiella burnetii with B-cell non-Hodgkin's lymphoma
89
how does Non-Hodgkins present?
painless lymphadenopathy - non tender, rubbery, asymmetrical
Constitutional/B symptoms (fever, weight loss, night sweats lethargy)
Extranodal disease
- gastric (dyspepsia, dysphagia, weight loss, abdominal pain),
- bone marrow (pancytopenia, bone pain, anaemia),
- lungs,
- skin,
-CNS (nerve palsies)
- compression symptoms e.g. gut obstruction, SVC obstruction, spinal cord compression
90
what investigations for Non-Hodgkin's lymphoma?
> FBC - thrombocytopenia, pancytopenia, lymphocytosis - may also be seen with various subtypes of NHL
> Lymph node biopsy - positive - certain subtypes will have classical appearance on biopsy such as Burkitt's lymphoma having a starry sky appearance
> Bone marrow biopsy
> Blood smear - nucleated red blood cells and left shift from bone marrow involvement
> LFTs - there may be liver involvement with lymphoma - so LFTs may be elevated
> LDH - may be elevated and indicated a worse prognosis
> CT/MRI chest, abdomen and pelvis for Ann arbor staging
91
how is Non-Hodkin's lymphoma managed?
Low grade (e.g. follicular lymphoma)
- if asymptomatic then likely no treatment will be given just monitoring
- radiotherapy may often be curative in localised disease
High grade - diffuse large B cell lymphoma, Burkitt's lymphoma
- chemotherapy plus Rituximab - R-CHOP
R = Rituximab (monoclonal antibody that targets CD20 on B cells)
C= cyclophosphamide
H = hydroxy-Daunorubicin
O= Vincristine - Oncovin is brand name
P = prednisolone
92
what are the complications of Non-Hodgkin's lymphoma?
```
bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
superior vena cava obstruction
metastasis
spinal cord compression
complications related to chemotherapy
```
93
what is Burkitt's lymphoma?
It is a high grade B-cell neoplasm
there are two major forms
- endemic (african) form - typically involves maxilla or mandible
- sporadic form - abdominal (e.g ileo-caecal) tumours are the most common form - most common in patients with HIV
94
what is myeloma?
myeloma is a haematological malignancy characterised by plasma cell proliferation.
Plasma cells are a type of B-lymphocyte that produce antibodies (immunoglobulins)
It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
95
how does myeloma present?
Four main features - hypercalcaemia, anaemia, renal impairment, bone pain
> hypercalcaemia occurs as a result of increased osteoclast activity within the bones - this leads to constipation, nausea, anorexia, confusion
> Renal - monoclonal production of immunoglobulins results in light chain deposition in the renal tubules, this causes renal damage which first presents as dehydrations and increased thirst. Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis.
> anaemia - bone marrow crowding suppresses erythropoiesis leading to anaemia which will cause fatigue and pallor
>bleeding - bone marrow crowding also results in thrombocytopenia which puts patients at risk of bleeding and bruising
> bones - bone marrow infiltration by plasma cells and cytokine-mediated oesteoclast overactivity creates lytic bone lesions - this may present as pain (especially in the back and increases the risk of fragility fractures)
> Infection - reduction in the production of normal immunoglobulins results in increased susceptibility to infection.
CRABBI - calcium, renal, anaemia, bleeding, bones, infection
96
what investigations would you perform for multiple myeloma?
Serum or urine electrophoresis (DIAGNOSTIC) - urine will have Bence Jones proteins, blood will have raised concentrations of monoclonal IgA/IgG proteins (monoclonal band of Ig in serum)
FBC - anaemia and thrombocytopenia
Serum calcium - raised
U&C - will show renal impairment
Bone marrow aspirate an d Biopsy - will show monoclonal plasma cell infiltration in the bone marrow
Serum free light-chain assay - increased concentrations of free light chain in serum
Serum albumin - raised
Serum beta2-microglobulin - a very strong predictor of multiple myeloma outcome
Skeletal survey - osteopenia, osteolytic lesions, pathological fractures
97
how would you treat multiple myeloma?
If suitable for stem cell transplant:
- induction therapy - Bortezomib and dexamethasone
- DVT prophylaxis - aspirin
- stem cell transplant
- for bone disease - bisphosphonates - zoledronic acid, and analgesics
If not appropriate for stem cell transplant:
- melphalan and prednisolone and thalidomide
DVT prophylaxis - aspirin
- stem cell transplant
- for bone disease - bisphosphonates - zoledronic acid, and analgesics
Complete remission is never attained and if patients stop treatment they will relapse.
98
what is hyperviscosity syndrome?
```
Hyperviscosity syndrome results from increased circulating serum immunoglobulins in Waldenstrom macroglobulinaemia and multiple myeloma, but may also occur in hyperproliferative states such as the acute leukaemias, polycythemia and the myeloproliferative disorders in which there are increased cellular blood components. As serum proteins or cellular components rise, the blood becomes more viscous, leading to the following clinical symptoms:
spontaneous gum bleeding
epistaxis
rectal bleeding
vertigo
hearing loss
paresthaesias
visual changes
headaches/seizures/ somnolence
heart failure
SOB
hypoxia
fatigue
```
99
what are complications of myeloma?
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Fractures of vertebral bodies
Peripheral neuropathy
hyperviscosity syndrome
renal failure
recurrent infections
cardiac failure
```
100
what staging system is used for multiple myeloma?
Durie and salmon staging system
101
what are the differentials for multiple myeloma?
Monoclonal gammopathy of undetermined significance (MGUS)
| Smouldering myeloma
102
what is MGUS?
Monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinaemia and monoclonal gammopathy) is a common condition that causes a paraproteinaemia and is often mistaken for myeloma. Differentiating features are listed below. Around 10% of patients eventually develop myeloma at 10 years, with 50% at 15 years
Features
usually asymptomatic
no bone pain or increased risk of infections
around 10-30% of patients have a demyelinating neuropathy
103
how do you differentiate 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)
104
what is smouldering myeloma?
It is where there is progression of MGUS with higher levels of antibody components. It is premalignant and more likely to progress to myeloma that MGUS.
Waldenstom's macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
105
what are causes of splenomegaly ?
```
CHICAGO
C - cancer
H - haematological malignancy
I - infection (CMV, HEP, HIV, TB, malaria, EBV) Inflammation - sarcoid, amyloid
C - congestion; portal hypertension
A- autoimmune (RA, SLE)
G - glycogen storage disorder
O - other - amyloidosis, sarcoidosis
```
Massive splenomegaly
- myelofibrosis
- CML
- visceral leishmaniasis
- malaria
- Gaucher's syndrome
106
what are some causes of lymphadenopathy?
```
Infective:
infectious mononucleosis
HIV, including seroconversion illness
eczema with secondary infection
rubella
toxoplasmosis
CMV
tuberculosis
roseola infantum
```
Neoplastic:
leukaemia
lymphoma
Others:
autoimmune conditions: SLE, rheumatoid arthritis
graft versus host disease
sarcoidosis
drugs: phenytoin and to a lesser extent allopurinol, isoniazid
