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8 Haematology
Fig 8.
https://t.me/med1917
66
Cutaneous T- cell lymphoma, which
has caused severe erythroderma (Sézary syndrome) in a Caucasian woman.
Fig 8.
istic jaw lymphadenopathy.
Courtesy of Prof. Christine Lawrence.
68
Burkitt’s lymphoma, with character-
Courtesy of Dr Tom D Thacher.
Fig 8.
67
(a, b) Villous lymphocytes (splenic
marginal zone lymphoma). (c) ‘Buttock cells’
with cleaved nuclei (follicular lymphoma). (d)
Sézary cells with convoluted nuclei.
Courtesy of Prof. Tangün & Dr Köroğlu.
361
Indications for treatment in indolent lymphoma
• Cytopenias secondary to BM infi ltrati on.
• Thre atene d end- organ function.
• Symptoms attributable to disease.
• Bulk at presentation.
• Steady progression during a period of observation >6 mon ths.
• Presentation with concurrent histologic transformation.
• Massive splenomegaly.
Fig 8.
69
Burkitt’s lymphoma, with three baso-
philic vacuolated lymphoma cells.
From the New England Journal of Medicine, Bain,
B, ‘Diagnosis from the blood smear’,
Copyright ©
2005
Reprinted with permission from Massachusetts
Massachusetts Medical Society.
353(5
Medical Society.
),
498
.
8 Haematology
The myeloproliferative disorders
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362
Caused by clonal proliferation of haematopoietic myeloid stem cells in the bone
marrow. These cells retain the ability to dierentiate into
causing an excess of one or more of these cell types (
Table 8.
10
Classification of myeloproliferative disorders
By proliferating cell type
RBC
WBC
Platelets Essential thrombocythaemia
Fibroblasts Myelofibrosis
Polycythaemia Refers to Hb >16.5 g/ dL in men or >16.0 g/ dL in women and/ or Hct
49
% in men or >48% in women (see
>
polycythaemia
depletion) or chronic (associated with obesity,
Absolute polycythaemia (
(plasma volume, normal
autologous radioactive chromium (
thaemia vera) or secondary due to hypoxia (eg high altitudes, chronic lung disease,
cyanotic congenital heart disease, heavy smoking) or inappropriately erythropoietin
secretion (eg
RCC, HCC
Polycythaemia vera The malignant proliferation of a clone derived from one pluri-
potent stem cell. A mutation in
progenitor ospring are unusual in not needing erythropoietin to avoid apoptosis.
There is exce ss proli feratio n of
and thrombosis. Commoner if >
detected on
FBC
, or present with vague symptoms due to hyperviscosity (p
headaches, dizziness, tinnitus, visual disturbance. Itching after a hot bath, and
erythromelalgia, a burning sensation in fingers and toes, are characteristic. Signs:
facial plethora and splenomegaly (in
turnover. Features of arterial (cardiac, cerebral, peripheral) or venous (
hepatic) thrombosis may be present.
WBC
and platelets. •
also
hyperplasia.
poietin.
a normal P
bosis. In younger patients at low risk, this is done by venesection. If higher risk (age
60
>
alfa is preferred in women of childbearing age. Ruxolitinib is
daily is also given.
• Cytogenetics as required to dierentiate from
• Raised red cell mass on 51Cr studies and splenomegaly, in the setting of
, is diagnostic. Tr eat me nt Aim to keep
aO2
yrs, previous thrombosis), hydroxycarbamide (= hydroxyurea) is used. Interferon
Prognosis Variable, many remain well for years. Thrombosis and
haemorrhage (due to defective platelets) are the main complications. Transition to
myelofibrosis occurs in ~
Essential thrombocythaemia (fig
leads to persistently platelets, often >
causing bleeding or arterial and venous thrombosis, and microvascular occlusion—
hypertension, ulceration, headache, atypical chest pain, erythromelalgia. Exclude
reactive causes of thrombocytosis (see
75
mg OD. Hydroxycarbamide in high- risk patients.
Aspirin
Myelofibrosis There is hyperplasia of megakaryocytes which produce platelet- de-
rived growth factor, leading to intense marrow fibrosis and haematopoiesis in the
spleen/ liver massive hepatosplenomegaly.
toms: night sweats, fever, weight loss; abdo discomfort due to splenomegaly; bone
marrow failure (Hb, infections, bleeding).
p
320
red cells,
diagnosis (
); characteristic teardrop
fig
8.72
). Tr ea tm ent Marrow support (p
plant may be curative in young people. Ruxolitinib, fedratinib, or hydroxycarbamide if
transplant ineligible and symptomatic
RBC
table
8.10
Polycythaemia vera (
Chronic myeloid leukaemia (
BOX
RBC
mass) is classically measured by dilution of infused
51
Cr)- labelled
PRV
)
CML
‘Investigating polycythaemia’). Relative
RBC
mass) may be acute (due to volume
HTN
, & alcohol/ tobacco intake).
RBCS
. Causes are primary (polycy-
).
JAK2 (JAK2 V617F
RBC
S,
60
yrs old. Presentation May be asymptomatic and
60
Investigations •
B
. • Marrow shows hypercellularity with erythroid
12
30
% or acute leukaemia in ~5%. Monitor
8.70
) is present in >95%. The erythroid
WBCS,
and platelets, leading to hyperviscosity
%). Gout may occur due to urate from
FBC: RCC,
CML
HCT
<0.45 to risk of throm-
) A clonal proliferation of megakaryocytes
1000
×
109/ L, with abnormal function,
BOX
‘Causes of thrombocytosis’). Treatment
Presentation Hypermetabolic symp-
Film Leukoerythroblastic cells (nucleated
RBC
S (fig
8.71
). Hb. Bone marrow trephine for
348
). Allogeneic stem cell trans-
Prognosis M edian surviva l 4– 5yrs.
S,
WBC
S, or platelets,
).
, p
356
)
368
DVT
Hb,
, cerebral,
HCT, PCV,
often
. • Serum erythro-
2
nd line. Aspirin 75mg
FBC
eve ry 3 mon ths.
RBC
):
8 Haematology
Investigating polycythaemia
https://t.me/med1917
• Initial investigations should include history, physical examination, pulse oxim-
FBC
, peripheral blood smear.
etry,
• Check if any evidence of volume depletion and thus, if Hb corrects with fluid
repletion.
• If polycythaemia vera suspected from presentation (eg tinnitus, itching,
erythromelalgia, etc.), send
• If not, check serum
• Is
EPO
in keeping with known cardiorespiratory disease? If not, check carboxy-
EPO
.
JAK2 V617F
mutation screen.
haemoglobin. Carboxyhaemoglobin suggests secondary polycythaemia due to
carbon monoxide toxicity from cigarette smoking or other exposure.
• If carboxyhaemoglobin is normal and no other clear explanation (eg post-
transplant erythrocytosis complicates
abdomen/ pelvis to rule out
MRI
• Seek Haematology advice.
10– 20
EPO
% of renal allograft), consider
- secreting tumour.
363
CT/
Causes of thrombocytosis
Platelets >
450
×
109/ L may be a reactive phenomenon, seen with many conditions
including:
• Bleeding. • Malignancy. • Post- surgery.
• Infection. • Trauma. • Iron deficiency.
• Chronic inflammation, eg collagen disorders,
Fig 8.
70
Essential thrombocythaemia: many
platelets seen.
© Prof. Christine Lawrence.
Fig 8.
72
Marrow trephine in myelofibrosis:
the streaming e ect is caused by intense fibrosis. Other causes of marrow fibrosis: any
myeloproliferative disorder, lymphoma, secondary carcinoma,
IBD
, coeliac disease.
Fig 8.
71
Teardrop cells, in myelofibrosis.
TB
, leukaemia, and irradiation.
© Prof. Christine Lawrence.
© Dr Nivaldo Medeiros.
8 Haematology
Paraproteinaemia
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364
Paraproteinaemia denotes the presence in the circulation of immunoglobulins produced by a single clone of plasma cells. The paraprotein is recognized as a monoclonal band (
1
M
band) on serum electrophoresis.10 There are six major categories:
Multiple myeloma See p
refers to the presence of
500
mg/ 24h and/ or marrow plasma cells 10– 60%,
>
(lytic lesions, anaemia, kidney disease, or hypercalcaemia) or other myeloma- defining events, and no amyloidosis
2
Wa lden str öm’s ma crog lob uli nae mia This is a lymphoplasmacytoid lymphoma
producing a monoclonal
CNS
and ocular symptoms. Lymphadenopathy and splenomegaly are also seen.
ESR
, with IgM paraprotein on serum electrophoresis. None if asymptomatic.
Combination chemotherapy (eg bendamustine + rituximab) may be used if
symptomatic. Plasmapheresis
3
Primary amyloidosis See ‘Amyloidosis’ (below).
4
Monoclonal gammopathy of uncertain significance See
5
Paraproteinaemia in lymphoma or leukaemia Eg seen in 5% of
6
Heavy chain disease Neoplastic cells produce free Ig heavy chains. - chain dis-
ease is most important, causing malabsorption from infiltration of bowel wall
(immunoproliferative small intestine disease—
Amyloidosis
This is a group of disorders characterized by extracellular deposits of a protein in
abnormal fibrillar form, resistant to degradation. The following are the systemic
forms of amyloidosis. Amyloid deposition is also a feature of Alzheimer’s disease,
2
diabetes mellitus, and haemodialysis- related amyloidosis.
type
AL
amyloid (primary amyloidosis) Insidious multisystemic debilitating disease.
Proliferation of plasma cell clone amyloidogenic monoclonal immunoglobulins
fibrillar light chain protein deposition organ failure death. Associations: mye-
15
%); Waldenström’s; lymphoma. Organs involved:
loma (
• Kidneys: glomerular lesions— proteinuria and nephrotic syndrome.
• Heart: restrictive cardiomyopathy (looks ‘sparkling’ on echo), arrhythmias, angina.
• Nerves: peripheral and autonomic neuropathy; carpal tunnel syndrome.
• Gut: macroglossia, malabsorption, haemorrhage, obstruction, hepatomegaly.
Autonomic neuropathy & delayed gastric emptying can lead to nausea/ weight.
• Vascular: purpura, especially periorbital— a characteristic feature (fig
Diagnosis often suspected late due to non- specific symptoms. Send serum free light
chain assay, serum & urine electrophoresis ± cardiac
SAP
) scan. Gold standard is tissue biopsy of kidney, fat pad, or bone marrow. Positive
(
Congo red staining with apple- green birefringence under polarized light microscopy.
Supportive care, nutrition, physiotherapy, disease education. First line; proteasome
inhibitor, eg bortezomib, with cyclophosphamide and dexamethasone (CyBorD). Anti-
CD
138
monoclonal antibodies, eg daratumumab eective in clinical trials. Aim for disease
reduction followed by high- dose melphalan with autologous stem cell transplantation.
Prognosis Median survival is 1– 2 years. Patients with myeloma and amyloidosis have
a shorter survival than those with myeloma alone.
AA
amyloid (secondary amyloidosis) Rare nowadays. Here amyloid is derived from
serum amyloid
toid arthritis,
bronchiectasis, osteomyelitis. It aects kidneys, liver, and spleen (
present with proteinuria, nephrotic syndrome, or hepatosplenomegaly. Macroglossia
is not seen; cardiac involvement is rare (ventricular hypertrophy and murmurs).
Manage the underlying condition optimally.
10
Electrophoresis and plasmapheresis look as though they should share endings, but they do not: Greek
phoros = bearing (esis = process), but aphairesis is Greek for removal.
A
, an acute phase protein, reflecting chronic inflammation in rheuma-
UC
/ Crohn’s, familial Mediterranean fever, and chronic infections— TB,
366
. Smouldering (asymptomatic) multiple myeloma
IgG
or IgA >3g/ dL or urinary monoclonal protein
IgM
paraprotein. Hyperviscosity is common (p
10
for hyperviscosity (p
AND
no end- organ damage
368
).
BOX
p
IPSID
). It may progress to lymphoma.
MRI
, serum amyloid protein P
fig 8.74), and may
365
CLL
8.73
368
.
.
), with
).
8 Haematology
Monoclonal gammopathy of uncertain significance (
https://t.me/med1917
MGUS
is a common (3% > 50yrs) but asymptomatic premalignant clonal plasma
cell or lymphoplasmacytic proliferative disorder. There is a paraprotein in the
3
g/ dL) but no myeloma, 1° amyloid, macroglobulinaemia, or lymphoma,
serum (<
with no bone lesions, no Bence Jones protein, and a low concentration of paraprotein, with <
common and may progress to myeloma,
macroglobulinemia), and light chain
multiple myeloma, AL amyloidosis).
phoresis, serum free light chain (
tory
MGUS.
10
% plasma cells in the marrow. Types Non- IgM
IgM MGUS
MGUS (LC- MGUS
Tests
SFL
) ratio, Ig levels, skeletal survey. Natural his-
(may progress to Waldenström
FBC, U&E,
Progress to more advanced disease at a rate of 1%/ year. IgM
Monitoring for progression Follow- up initially at 3– 6 months to recheck
MGUS
)
MGUS
is most
; may progress to light chain
2
+
Ca
, serum & urine electro-
MGUS >
non- IgM
labs and ask if any red flag symptoms/ signs have developed (eg bone pain, ‘
symptoms, lymphadenopathy, etc.). If asymptomatic and low- risk labs (eg
type, serum monoclonal protein <
up necessary. Check with Haematology if in doubt. Be aware that
associated with increased risk of osteoporosis and
Fig 8.
73
Periorbital purpura in amyloidosis.
© Prof. Christine Lawrence.
1.5
g/ dL or normal
SFL
ratio), only annual follow-
VTE
. Consider
DEXA
MGUS
.
is also
IgG
B
365
’
Fig 8.
74
Areas of amyloid deposition
in liver and spleen in amyloidosis
(isotope scan).
Reproduced from Warrell et al., Oxford
Textbook of Medicine,
permission from Oxford University Press.
2010
, with
8 Haematology
Myeloma: the chief plasma cell dyscrasia (
PCD
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366
PCD
S are due to an abnormal proliferation of a single clone of plasma or lympho-
plasmacytic cells leading to secretion of immunoglobulin (
causing the dysfunction of many organs (esp. kidney). The
clonal band, or paraprotein, on serum or urine electrophoresis.
Classification Based on Ig product— IgG in ~ ⅔; IgA in ~ ⅓; a very few are IgM or
IgD
. Other Ig levels are low (‘immunoparesis’, causing susceptibility to infection). In
⅔, urine contains Bence Jones proteins, which are free
~
or lambda (λ) type, filtered by the kidney.
Incidence 5/
100 000
Clinical features • Osteolytic bone lesions cause backache, pathological fractures, &
vertebral collapse.
• Hypercalcaemia may be symptomatic (p
vation, from signalling by myeloma cells.
• Anaemia, neutropenia, or thrombocytopenia may result from marrow infiltration
by plasma cells, leading to symptoms of anaemia, infection, and bleeding.
• Recurrent bacterial infections due to immunoparesis, and also because of neutro-
penia due to the disease and from chemotherapy.
• Kidney disease seen in ~20% at diagnosis (p
due to light chain cast nephropathy (‘myeloma kidney’). Light chains have a toxic/
Do serum electrophoresis on all >50yrs with new back pain.
inflammatory eect on the proximal tubule, but main eect is due to precipitation
in the distal loop of Henle. Deposits may rarely be
syndrome, see
clonal
• Neuropathy sensory ± motor— uncommon at the time of diagnosis and mostly
p
364
I
g deposition disease. May also be related to Ca2, contrast, or meds.
due to amyloidosis.
Tests Bloods
Persistently
unless healing fracture.
Serum & urine electrophoresis, serum free light chain ratio, 2- microglobulin
test
(prognostic),
FBC:
normocytic normochromic anaemia. Film: rouleaux (p
ESR
(p
368
LDH
. Imaging Skeletal survey: X- rays of chest; all of spine; skull; pelvis
may show lytic ‘punched- out’ lesions, eg pepper- pot skull, vertebral collapse, fractures, or osteoporosis.
Diagnostic criteria See
Treatment Supportive • Analgesia for bone pain (avoid
AKI
). Give all patients a bisphosphonate (sodium clodronate, zoledronic acid, or
pamidronate disodium), as they reduce fracture rates and bone pain, and increase
survival. Local radiotherapy can help rapidly in focal disease. Orthopaedic procedures (vertebroplasty or kyphoplasty) may be helpful in vertebral collapse.
should be corrected with transfusion, and erythropoietin may be used.
hydrate, and ensure adequate fluid intake of
Dialysis may be needed in
biotics until culture results are known. Regular
needed if recurrent.
Chemotherapy Induction therapy with, eg lenalidomide, bortezomib, and dexa-
methasone. In suitably fit patients this may be followed by autologous stem- cell
transplantation. In those unsuitable for transplantation, induction therapy is typically continued for
Treatment is then typically held until (inevitably) paraprotein levels start to rise
again, at which point further chemotherapy or stem cell transplantation may be
considered.
SE
, notably neutropenia and thromboembolism: monitor for sepsis and consider as-
12– 18
NB
: lenalidomide is a teratogenic immunomodulator which has multiple
pirin or anticoagulation if risk , eg hyperviscosity or other comorbidities.
Prognosis Worse if: >2 osteolytic lesions, 2- microglobulin >5.5mg/ L, Hb <11g/ L;
30
albumin <
cytogenetic abnormalities associated with high risk of progression. Causes of death:
infection,
g/ L. Risk stratification increasingly based upon detection of specific
AKI
.
)
I
g) or an Ig fragment,
I
g is seen as a mono-
I
g light chains of kappa (κ)
. Peak age: 70yrs. : ≈ 1:1. Afro- Caribbeans:Caucasians ≈ 2:1.
668
). Lesions are due to osteoclast acti-
310
, p
364
). Multiple causes but often
AL
- amyloid (causing nephrotic
) or else monoclonal Ig can disrupt glomeruli to cause mono-
2
). Urea and creatinine, Ca
+
(in ~40%). Alk phos usually
Bone marrow biopsy See figs
CT
or
MRI
may be useful to detect lesions not seen on X- ray.
BOX
‘Myeloma diagnosis’.
NSAID
8.75– 8.78
S due to risk of
320
. Screening
• Anaemia
•
AKI
3
AKI
. • Infections: treat rapidly with broad- spectrum anti-
L/ day to prevent cast nephropathy.
IV
immunoglobulin infusions may be
: re-
months, or until serum paraprotein levels have plateaued.
).
8 Haematology
AKI
Myeloma diagnosis
https://t.me/med1917
Diagnostic criteria: ≥ 10% marrow
plasma cells or extramedullary
plasmacytoma and at least one of
the following:
1
Evidence of end- organ damage
from myeloma:
• Hypercalcaemia.
• Renal insuciency.
• Anaemia.
• Bone lesions: do skeletal
survey ± whole- body
PET- CT
2
.
Myeloma- defining biomarkers:
>60
% bone marrow plasma cells,
serum free light ratio
focal lesion on
MRI.
>100
MRI
, or >1
and
Causes of bone pain/ tenderness
• Trau ma / fracture (steroids risk) .
• Myeloma and other primary malig-
nancy, eg plasmacytoma or sarcoma.
• Secondaries (eg from breast, lung, etc.).
• Osteonecrosis, eg from microemboli.
• Osteomyelitis/ periostitis (eg syphilis).
• Hydatid cyst (bone is a rare site).
• Osteosclerosis, eg from hepatitis C.
• Page t’s dise ase of b one.
• Sickle cell anaemia.
• Renal osteodystrophy.
•
CREST
syn drome/ Sjögren’s syndrome.
• Hyperparathyroidism.
Te st s
PSA, ESR
, Ca
2
+
,
LFT,
ele ctrop horesi s.
Tre at me nt Treat the cause; bisphospho-
& NSAID
nates
S may c ontrol sym ptoms .
Complications of myeloma
• Hypercalcaemia (p
or relapse. Rehydrate vigorously with
IV
bisphosphonates, eg zoledronic acid or pamidronate disodium, are useful for
) This occurs with active disease, eg at presentation
IV
fluids 4– 6L/ d (careful fluid balance).
treating hypercalcaemia acutely.
• Spinal cord compression (p
MRI
if suspected. Treatment is with dexamethasone 8– 16mg/ 24h PO and local
radiotherapy.
• Hyperviscosity (p
cognition, disturbed vision, and bleeding. It is treated with plasmapheresis to
remove light chains.
•
is treated with rehydration. Urgent dialysis may be needed.
462
) Occurs in 5% of those with myeloma. Urgent
368
) occurs particularly with Ig
M, IgA, IgG3.
Causes reduced
367
Fig 8.
75
Myeloma bone marrow: many
plasma cells with abnormal forms.
Courtesy of Prof. Christine Lawrence.
1
2
3
4
5
6
7
SPE IgGIgMIgA
Fig 8.
77
An IgG kappa paraprotein
monoclonal band (immunofixation electrophoresis; a control sample has run on
the left).
Courtesy of Prof. Christine Lawrence.
Fig 8.
76
Marrow section in myeloma, stained
IgG
kappa monoclonal antibody.
with
Fig 8.
smear. (b) Peripheral smear. Note rouleaux formation of red cells (
Courtesy of Prof. Christine Lawrence.
(a) (b)
78
Plasma cells in myeloma. (a) Marrow
p
320
, p
366
Courtesy of Prof. Tangun & Dr Köroğlu.
).
8 Haematology
Erythrocyte sedimentation rate (
ESR
ESR
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368
The
ESR
is a sensitive but non- specific indicator of the presence of disease. It meas-
RBC
ures how far
S fall through a column of anticoagulated blood in
proteins cover red cells, these cause
same phenomenon as rouleaux,
Causes of a raised
Any inflammation (eg infection, rheumatoid arthritis, malig-
p
320
)
RBC
S to stick to each other in columns (the
) so they fall faster.
nancy, myocardial infarction), anaemia, and macrocytosis.
Caveats •
upper limit of normal in older patients: :
• Some conditions lower the
microcytosis, and sickle cell anaemia. Even a slightly raised
ESR
with age. The Westergren method is a rough guide to calculate the
ESR
ESR
= age ÷ 2; :
ESR
= (age + 10) ÷ 2.
, eg polycythaemia (due to red cell concentration),
ESR
should prompt one to ask: ‘What else is the matter?’
Management • In those with a slightly raised
wait a month and repeat the test.
can have a
90
% predictive value for disease, so such patients should be thoroughly
• If the
investigated, even in the presence of non- specific symptoms. Take a full history,
examine carefully, and consider these tests:
chest and abdominal imaging, ± biopsy of bone marrow or temporal artery.
ESR,
the best plan is probably to
ESR
is markedly raised (>
FBC
, plasma electrophoresis,
Plasma viscosity (PV)
Normal range: 1.50– 1.72mPa/ s. In many labs, this has replaced the
aected by anaemia and simpler to automate.
tion of large plasma proteins and in the same conditions as the
ESR
in chronic inflammation and are less aected by acute changes (unlike
and
CRP,
p
678
).
PV
is aected by the concentra-
Hyperviscosity syndrome
Symptoms Lethargy; confusion; cognition
disturbance; chest pain; abdominal
CNS
pain (and sometimes spontaneous
bleeding); syncope; visual disturbance (eg
vision, amaurosis fugax, retinopathy— eg engorged retinal veins, haemorrhages, exudates;
and a blurred disc as seen in
symptoms are like ‘looking through a watery
fig
8.79
). The visual
car windscreen’.
Causes of high blood viscosity Very high red cell count (haematocrit >50,
eg polycythaemia vera), white cell count (>
plasma components— usually immunoglobulins, in myeloma or Waldenström’s
macroglobulinaemia (
amount of
IgG
p
364
, as IgM is larger and so viscosity more than the same
). Drugs: eg diuretics, IV Ig, erythropoietin, chemotherapy, radio- con-
trast media.
Treatment Urgent treatment is needed which depends on the cause. Venesection
is done in polycythaemia. Leukapheresis in leukaemias to remove white cells.
Plasmapheresis in myeloma and Waldenström’s: blood is withdrawn via a plasma
exchange machine, the supernatant plasma from this is discarded, and the
returned to the patient after being resuspended in a suitable medium.
GI
or GU
;
Fig 8.
79
Hyperviscosity syndrome.
100
×
109/ L, eg leukaemia), or
1
h. If certain
in these patients
100
mm/ h), this
U&E, PSA
ESR
, as it is less
ESR
— both PV
RBC
,
S
8 Haematology
The spleen and splenectomy
OHCS
https://t.me/med1917
The spleen plays a vital immunological role by acting as a reservoir for lymphocytes, and in dealing with bacteraemias.
Causes of splenomegaly (See also p
596
.) Massive (enlarged to the
RIF
):
myelofibrosis, malaria (hyperreactive malarial splenomegaly), visceral leishmaniasis, ‘tropical splenomegaly’ (idiopathic— Africa, south- east Asia), and Gaucher’s
syndrome. Moderate:
schistosomiasis).
lytic anaemia, leukaemia especially
RA, SLE
). • Others: sarcoidosis, primary antibody deficiency (
(
• Infection (eg
EBV
, endocarditis,
TB,
malaria, leishmaniasis,
• Portal hypertension (liver cirrhosis). • Haematological (haemo-
CML
, lymphoma). • Connective tissue disease
p
244
), idiopathic.
When is a mass in the left upper quadrant a spleen? (Main dierential: enlarged
left kidney.) The spleen:
down on inspiration.
• You may feel a medial notch. • ‘You can’t get above it’ (ie the
• Is dull to percussion. • Enlarges towards the
RIF.
• Moves
top margin disappears under the ribs).
Tests Image the spleen with abdominal
ment: look for lymphadenopathy and liver disease, eg:
USS
or
CT.
Hunt for the cause of enlarge-
FBC, ESR, LFT
± liver, marrow,
or lymph node biopsy.
Complications Symptoms of anaemia, infection, or bleeding can occur as a result
of hypersplenism: cells become trapped in the spleen’s reticuloendothelial system
causing pancytopenia. Splenectomy may be required if severe.
Splenectomy Main indications: splenic trauma, hypersplenism, autoimmune
ITP
(p
343
haemolysis: in refractory
p
334
), or congenital haemolytic anaemias. Mobilize early post- splenectomy as
(
), warm autoimmune haemolytic anaemia
transient platelets predisposes to thrombi. A characteristic blood film is seen following splenectomy, with Howell– Jolly bodies, Pappenheimer bodies, and target
p
320
).
cells (
The main problem post- splenectomy is lifelong increased risk from infection.
The spleen contains macrophages which filter and phagocytose bacteria. Postsplenectomy infection is caused most commonly by encapsulated organisms:
Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.
Reduce this risk by giving:
1
Immunizations:
• Pneumococcal vaccine (p
sponse, or as soon as possible after emergency splenectomy, eg after
trauma. Re- immunize every
• Haemophilus influenzae type b vaccine (Hib, see p
• Meningococcal vaccination course, including Men
• Annual influenza vaccine (p
2
Lifelong prophylactic oral antibiotics: phenoxymethylpenicillin (penicillin V) or
erythromycin if penicillin allergic.
3
Pendants, bracelets, or patient- held cards to alert medical sta.
4
Advice to seek urgent medical attention if any signs of infection: will require
admission for broad- spectrum antibiotics if infection develops.
5
If travelling abroad, warn of risk of severe malaria and advise meticulous
prophylaxis, with nets, repellent, and medication.
169
), at least 2 weeks pre- op to ensure good re-
5– 10
yrs. Avoid in pregnancy.
392
).
387
).
B
, Men C, and Men
ACWY
The advice given here also applies to hyposplenic patients, eg in sickle cell anaemia or coeliac disease.
CML
369
,
.
8 Haematology
Thrombophilia
APC
OHCS
https://t.me/med1917
370
Thrombophilia is an inherited or, more commonly, acquired coagulopathy that
DVT
predisposes to thrombosis, usually venous:
voked or unprovoked. Special precautions are needed when there is an additional
risk factor for thrombosis, eg surgery, pregnancy (see
50
% of patients with thrombosis and a + ve family history have an identifi-
Only ~
or PE. Determine if event was pro-
BOX
for other risk factors).
able thrombophilia on routine tests: others may have abnormalities that are as yet
unidentified.
Inherited
• Activated protein C (
thrombophilia. Present in ~
thrombosis. Usually associated with a single point mutation in factor
Leiden), so that this clotting factor is not broken down by
5
- fold if heterozygous for the mutation (50- fold if homozygous). Thrombotic
raised
risk is increased in pregnancy and those on oestrogens (
• Prothrombin gene mutation Causes high prothrombin levels and thrombosis
due to down- regulation of fibrinolysis, by thrombin- activated fibrinolysis inhibitor.
• Protein C & S deficiency These vitamin K- dependent factors act together to cleave
and so neutralize factors
) resistance/ factor v Leiden Chief cause of inherited
5
% of the population, although most will not develop
APC
. Risk of
p36, p
V
&
VIII
. Heterozygotes deficient for either protein risk
thrombosis. Skin necrosis also occurs (esp. if on warfarin). Homozygous deficiency
for either protein causes neonatal purpura fulminans— fatal, if untreated.
• Antithrombin deficiency Antithrombin is a co- factor of heparin, and inhibits
thrombin. Less common, aects
than protein
C
or S deficiency by ~4- fold. Homozygosity is incompatible with life.
1:500
. Heterozygotes’ thrombotic risk is greater
Acquired Causes • Surgery • Cancer (Khorana score can help predict risk of
8
in cancer patients).
• Oestrogen- containing oral contraceptive pills/
• Antiphospholipid syndrome (
of thrombocytosis or polycythaemia may also cause thrombosis (
Which tests? Ask the lab. Do
APC
resistance test, lupus anticoagulant and anticardiolipin antibodies, and assays
±
for antithrombin and proteins
V
Leiden mutation if
FBC,
film, clotting (PT, thrombin time,
C
APC
& S deficiency (±
resistance test is + ve, and for prothrombin gene mutation).
APLS
: see
BOX
, p
HRT
(relative risk 2– 4). • Any cause
552
p
DNA
analysis by
PCR
These tests should ideally be done when the patient is well, not pregnant, and o
1
anticoagulation for
month.
Who? Test those with: • arterial thrombosis or MI at <50yrs old (eg for
VTE
provoked
pregnancy
thrombosis
(ie at <40yrs with no risk factors) •
• unexplained recurrent
VTE
• unusual site, eg mesenteric or portal vein
• recurrent fetal loss (≥3) • neonatal thrombosis.
VTE
with oral contraceptives/
Who not? Those already on lifelong anticoagulation, 1st- degree relatives of people
DVT/ PE
with a history of
or thrombophilia except in special circumstances. There is
often no benefit to testing (ie no change to management), it is expensive and may
cause significant worry to patients: be sparing in requesting these tests.
Treatment Anticoagulate acute thrombosis (p
346
). If recurrence occurs with no
other risk factors, consider lifelong anticoagulation. Recurrence whilst on treatment should be treated by increasing treatment intensity (eg target
antithrombin deficiency, high doses of heparin may be needed; liaise with a haematologist. In protein
occur with warfarin.
C
or S deficiency, monitor treatment closely as skin necrosis may
Prevention Lifelong anticoagulation is not needed in absence of
of risk with oestrogen-containing oral contraceptive pill or
HRT
regards to the best form of contraception. Warn about other risk factors for
Prophylaxis may be needed in pregnancy, eg in antiphospholipid syndrome (get
expert help: aspirin and, sometimes, prophylactic heparin are used as warfarin is
teratogenic, see
risk situations, eg pre- surgery.
OHCS
p36). Prophylactic SC heparin may also be indicated in high-
V
(factor V
DVT
or PE is
121
, & p
155
).
VTE
) • Pregnancy.
362
).
APTT
, fibrinogen)
for the factor
APL
) • un-
INR
to 3– 4). In
VTE
, but advise
, and counsel as
VTE
.
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