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8 Haematology
Table 8.
https://t.me/med1917
3
Clotting screen abnormalities in coagulopathies
Disorder
Heparin
DIC
Liver disease
Platelet defect
K
deficiency
Vit
Haemophilia
von Willebrand’s
INR APTT
/ /
Special tests may be available (factor assays: consult a haematologist).
Thrombin time Platelet count Notes
D
- dimer, p
AST
See
See
340
p
342
p
698
Thrombocytopenia
Platelet count <
counts <
Causes Many: drug- induced, heparin- induced (
DIC
, liver disease, pregnancy (gestational, pre-eclampsia, etc.),
leukaemia, lymphoma,
If thrombocytopenia + thrombosis, consider
syndrome or more rarely, paroxysmal nocturnal haemoglobinuria
Evaluation As per p
150 000
10 000
/ microlitre but risk of spontaneous bleeding greatest with
/ microlitre, and surgical bleeding with counts <50
HIT,
B
/ folate deficiency,
12
340
— bleeding, past medical history, family history, medica-
HIV.
DIC, HIT,
000
p
347
), sepsis or cancer with
ITP
/ microlitre.
(p
343
)
, TTP, HUS,
antiphospholipid antibody
.
tions, petechiae/ purpura, lymphadenopathy, hepatosplenomegaly.
Tests
FBC
, film (pseudothrombocytopenia can occur with platelet clumping), co-
U&E, LFT
agulation screen,
antiphospholipid Abs,
S ± fibrinogen, haemolysis screen,
B
/ folate, bone marrow biopsy as appropriate.
12
HIV/ HCV
testing,
Management Depends on the cause but urgent action (and haematology con-
50 000
sult) needed if platelet count <
pregnant, suspected
HIT, TTP, HUS,
/ microlitre, planned invasive procedure, if
drug- induced thrombotic microangiopathy,
acute leukaemia, or aplastic anaemia. Seek expert advice if considering stopping
antiplatelets/ anticoagulants or planning invasive procedure.
ANA
341
,
8 Haematology
Bleeding disorders
OHCS
OHCS
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342
After injury, three processes halt bleeding: vasoconstriction, gap- plugging by platelets, and the coagulation cascade (
three groups. The pattern of bleeding is important— vascular and platelet disorders
lead to prolonged bleeding from cuts, bleeding into the skin (eg easy bruising and
purpura), and bleeding from mucous membranes (eg epistaxis, bleeding from gums,
menorrhagia). Coagulation disorders cause delayed bleeding into joints and muscle.
1
Vasc ular de fec ts Congenital Osler– Web er– Rendu syndrome (p
tissue disease (eg Ehlers– Danlos syndrome,
Acquired Senile purpura, infection (eg meningococcal, measles, dengue fever), ster-
oids, scurvy (perifollicular haemorrhages), Henoch– Schönlein purpura (
2
Platelet disorders Decreased marrow production Aplastic anaemia (p
megaloblastic anaemia, marrow infiltration (eg leukaemia, myeloma), marrow
suppression (cytotoxic drugs, radiotherapy).
thrombocytopenia (
causes, eg
thrombocytopenic purpura (
Poorly functioning platelets Seen in myeloproliferative disease,
3
Coagulation disorders Congenital Haemophilia, von Willebrand disease.
ITP
SLE, CLL
, drugs, eg heparin, viruses; Non- immune:
Acquired Anticoagulants, liver disease,
Haemophilia A Factor
1:10 000
male births. There is a high rate of new mutations (30% have no family
in
Presentation depends on severity and is often early in life or after surgery/
history).
trauma— with bleeds into joints leading to crippling arthropathy, and into muscles
causing haematomas (pressure can lead to nerve palsies and compartment syn-
ICH
drome).
factor
jections (
0.3
(
bleeds (eg haemarthrosis): factor
factor
Genetic counselling
is relatively rare but can be life- threatening. Diagnose by
VIII
assay (<40%). Management Seek expert advice. Avoid
fig
8.46
mcg/ kg/ 12h
). Minor bleeding: pressure and elevation of the part. Desmopressin
IVI
over 20min) raises factor
VIII
. Life- threatening bleeds (eg obstructing airway) need levels of
Haemophilia B (Christmas disease) Factor IX deficiency (inherited, X- linked reces-
sive); behaves clinically like haemophilia
Von Willebrand disease (vWD) Most common inherited haemostatic disorder (up
1
% prevalence). Von Willebrand factor (vWF) has three roles in clotting: 1 To bring
to
platelets into contact with exposed subendothelium.
each other.
tion. There are >
WF.
v
3
To bind to factor
22
types of vWD; the commonest are: Type I (60– 80%) Levels of
Symptoms are mild. Autosomal dominant. Type II (20– 30%) Abnormal v
with lack of high- molecular- weight multimers. Usually autosomal dominant inheritance. Bleeding tendency varies.
somal recessive with gene deletions). v
Symptoms can be severe.
tooth extraction.
(functional assay);
mild bleeding, v
NSAID
Avoid
Tests
WF-
containing factor
S. Risk of postpartum haemorrhage.
Acquired haemophilia often presents with large mucosal bleeds. Caused by sud-
denly appearing autoantibodies that interfere with factor
autoantibody; factor
Liver disease Produces a complicated bleeding disorder with synthesis of clotting
factors, absorption of vitamin
Malabsorption Leads to less uptake of vitamin K (needed for synthesis of factors
II, VII, IX
, and X). Treat with IV vitamin K (10mg). In acute haemorrhage, use human
prothrombin complex or fresh frozen plasma.
fig
8.45
). Disorders of haemostasis fall into these
694
p
846
, pseudoxanthoma elasticum).
), connective
p
307
).
Excess destruction Immune: immune
, see
BOX
‘Immune thrombocytopenia’), other autoimmune
TTP
), or
HUS (
p
311
), sequestration (in hypersplenism).
DIC
(p
350
VIII
deficiency; inherited in an X- linked recessive pattern
VIII
levels to 50% of normal, eg with recombinant
p
274
.
VIII,
protecting it from destruction in the circula-
), vitamin K deficiency.
VIII
levels, and may be sucient. Major
A
. Treat with recombinant factor
DIC
(p
350
), thrombotic
NSAID
S, and urea.
APTT
NSAID
S and
IX.
2
To make platelets bind to
Type III (1– 5%) Undetectable vWF levels (auto-
WF
antigen is lacking and there is factor
Signs bruising, epistaxis, menorrhagia, bleeding post-
APTT
, factor
VIIIC
INR
and platelets. Get expert help. Desmopressin is used in
VIII
activity <50%. Steroids.
K
(clotting activity), vWF Ag and activity
VIII
concentrate for surgery or major bleeds.
VIII
. Tests
, and abnormalities of platelet function.
APPT
IM
100
;
348
and
in-
%.
WF,
VIII
VIII
),
.
343
8 Haematology
https://t.me/med1917
Fig 8.
45
Intrinsic and extrinsic pathways of coagulation (simplified!).
Fibrinolysis
The fibrinolytic system works by generating plasmin, which causes fibrin dissol-
ution. The process starts with the release of tissue plasminogen activator (t
endothelial cells, a process stimulated by fibrin formation. tminogen to plasmin which can then cleave fibrin, as well as several other factors. tand plasminogen both bind fibrin thus localizing fibrinolysis to the area of the clot.
Fibrinolytic agents activate this system and can be utilized in order to break
down pathological thrombi, eg acute ischaemic stroke,
inal venous or arterial thrombosis. In all cases the risk of adverse eects of
thrombolysis (eg haemorrhage) must be outweighed by the potential benefits.
Streptokinase, a streptococcal exotoxin that binds and activates plasminogen,
was the first licensed agent but risks anaphylaxis on repeat dosing. Alteplase is
recombinant t-
PA.
Newer agents include tenecteplase and reteplase.
Immune thrombocytopenia (
Primary
ITP
T
cells. There is both platelet destruction and underproduction. It is acute (usu-
ally in children,
is caused by antiplatelet autoantibodies and autoreactive cytotoxic
2
wks after infection with sudden self- limiting purpura) or chronic
(seen mainly in women). Chronic
pura, epistaxis, and menorrhagia. There is no splenomegaly. In secondary
there is an underlying associated condition (eg
ITP
induced
marrow. Rule out other causes of platelets.
platelets <
keep platelets >
include vancomycin, carbamazepine, etc. Tests Megakaryocytes in
20
×
109/ L, prednisolone 1mg/ kg/ d and reduce after remission; aim to
30
×
109/ L— takes a few days to work. Platelet transfusions are
not used (except during splenectomy or life- threatening haemorrhage) as these
are quickly destroyed by the autoantibodies.
raise the platelet count, eg for surgery, pregnancy. If relapse or poor response to
initial treatment, choices include
12
mths before considering as may spontaneously remit). Eltrombopag/
(wait
avatrombopag and romiplostim are also licensed as second- line therapies that
stimulate proliferation and dierentiation of megakaryocytes. Vaccine- induced
ITP (IVITT
) is a rare side eect of certain adenoviral- vectored
that can present with thrombosis (esp.
Fig 8.
46
Mild haemophilia after an
tion.
etc.
PA
converts inactive plas-
DVT, PE
, and central ret-
ITP
)
ITP
runs a fluctuating course of bleeding, pur-
SLE, HIV)
and causes of drug-
IM
Give vaccines
SC
!
© Crookston
Collection
- PA
) from
None if mild. If symptomatic or
IV
immunoglobulin may temporarily
B
- cell depletion with rituximab or splenectomy
COVID- 19
CVST
) or thrombocytopenia.
vaccines
injec-
PA
ITP
53
,
.
8 Haematology
Blood transfusion and blood products
FFP
CMV
https://t.me/med1917
344
Blood should only be given if strictly necessary and there is no alternative.
Outcomes may be worse after an inappropriate transfusion.
• Know and use local procedures to ensure that the right blood gets to the right pa-
tient at the right time.
• Take blood for crossmatching from only one patient at a time. Label immediately.
This minimizes risk of wrong labelling of samples.
• When giving blood, monitor T°, pulse, RR, and BP every ½h.
• Use a dedicated line where practicable (or dedicated lumen of multilumen line).
Products4 Red cells (Packed to make haematocrit ~70%.) Use to correct anaemia or
1U Hb by 10– 15g/ L. In anaemia, transfuse until Hb ~80g/ L. Platelets (p
blood loss.
Usually only needed if bleeding or count is <
20
×
109/ L. Failure to do so suggests refractory cause: discuss with haematologist.
>
If surgery is planned, get advice if count is <
Use to correct clotting defects: eg
to prevent dilutional coagulopathy; liver disease; thrombotic thrombocytopenic pur-
p
311
). It is expensive and carries all the risks of blood transfusion. Do not use
pura (
as a simple volume expander.
protein solution and is used to replace protein.
in the hypoproteinaemic patient (eg liver disease; nephrosis) who is fluid overloaded,
without giving an excessive salt load. Also used as replacement in abdominal para-
p
749
centesis (
X
; for rapid reversal of anticoagulants eg warfarin) Cryoprecipitate (a source of fi-
). Others Prothrombin complex concentrate (contains factors II,
brinogen); coagulation concentrates (self- injected in haemophilia); immunoglobulins.
Irradiated blood products To prevent graft- vs- host disease (
compromised host, eg severe
of allogeneic haemopoietic stem cell transplantation, Hodgkin’s lymphoma, those
treated with purine analogue drugs (eg fludarabine). Check with Haematology if
unsure.
- negative blood Required if pregnant, immunosuppressed, eg bone marrow,
stem cell, solid organ recipients,
Complications of transfusion Management of acute reactions:4 see
‘Transfusion reactions’ and
• Early (within 24h) Acute haemolytic reactions (eg
phylaxis (may be due to anti-
IgA
in the transfusion or due to allergies to another constituent in the trans-
with
fused product); bacterial contamination (sepsis); febrile reactions (eg from release
of cytokines from
tions (itch, urticaria, mild fever); transfusion- associated circulatory overload (
may occur if
WBC
RBC
S given too rapidly or if underlying cardiac disease); transfusion-
related acute lung injury (
plasma; can be life- threatening).
sion, diuretic response, cardiac history, older age or large transfusion volume.
• Delayed (after 24h) Infections (eg viruses: hepatitis
prions); delayed haemolytic reactions, iron overload (treatment,
transfusion purpura— rare bu t potentia lly letha l fall in plate let count
transfusion requiring specialist treatment with
Massive blood transfusion This is defined as replacement of an individual’s entire
blood volume (>
+
; hypothermia. For emergency management, see p
K
support from haematologist & blood bank who should advise on products and
10U) within 24h. Complications: platelets; Ca
monitoring. In acute haemorrhage, use crossmatched blood if possible, but if not,
use ‘universal donor’ group O Rh–ve blood, changing to crossmatched blood as soon
as possible.
Transfusing patients with heart failure Give each unit over 3– 4h with fur-
40
osemide (eg
JVP
and basal lung crackles; consider
mg slow
20
×
109/ L.
1U should platelet count by
100
×
DIC
109/ L. Fr esh f roz en pl asm a (
(p
350
); as part of massive transfusion protocol
Human albumin solution is produced as 4.5% or 20%
20
% albumin can be used temporarily
VII, IX
GVHD
348
T
- lymphocyte immunodeficiency syndromes, recipients
HIV
- positive patients.
table
8.4
.
IgA
antibodies in IgA- deficient individuals that react
S in a product that has not been leukoreduced); allergic reac-
TRALI
, ie
ARDS
TAC O
more likely than
ABO
or Rh incompatibility); ana-
due to antileucocyte antibodies in donor
TRALI
B/ C, HIV
IVIG
and platel et tran sfusio ns.
774
IV/ PO
; don’t mix with blood) with alternate units. Check for
CVP
line.
) in an immuno-
BOX
TAC O
if no fever, hyperten-
; bacteria; protozoa;
p
338
);
GVHD
; post-
5– 7
d post-
2
+
; clotting factors;
. Seek early & ongoing
.)
)
,
;
8 Haematology
Acute transfusion reactions
STOP
STOP
STOP
STOP
STOP
SLOW
STOP
SLOW
STOP
SLOW
STOP
https://t.me/med1917
All UK blood products are now leucocyte- depleted (white cells <5 ×
reduce the incidence of complications such as alloimmunization to
antigens and febrile transfusion reactions. Consider an acute transfusion reaction
if adverse symptoms/ signs within
minutes. Initially
examine for fever, hypo/ hypertension, respiratory distress, urticaria, angioedema.
Get senior help in all cases. Significant BP suggestive of acute haemolytic reac-
tion,
transfusion. Ensure IV access, correct product for patient,
TRALI
, and sepsis. Remember isolated fever may be related to a pre- existing
24
h though many happen within the first 15
106/ L) to
HLA
class I
diagnosis of sepsis (get history, look at temperature trend).
Table 8.
4
Management of transfusion reactions
Acute haemolytic reaction
(eg
ABO
incom patibility) Agit ation, T°
BP
(rapid onset),
, flushing, abdominal/
chest pain, oozing venepuncture sites,
Anaphylaxis
Bronchospasm, cyanosis, BP, soft tissue
swelling
Bacterial contamination (transfusionassociated sepsis)
T° (rapid onset),
BP,
and ri gors
Tra ns fu sio n- re la te d l un g in ju ry (
(See p
344
.) Dyspnoea, cough, fever;
‘white out’
Non- haemolytic febrile transfusion
reaction
Dx of exclusion. More common with
Shivering and fever usually ½–
1
h after
transfusion. Check identity and name
on unit; tell haematologist; send unit +
U&E
, clotting, cultures, & urine (haemo-
DIC
globinuria) to lab. Keep
crystalloids
. Treat
the transfusion. Maintain airway and
IV
DIC
(p
350
give oxygen. Adrenaline, antihistamines,
pressors. Contact anaesthetist.
the transfusion. Check identity against
name on unit; tell haematologist and send
FBC, U&E
unit +
lab. Start broad- spectrum antibiotics
TRALI)
CXR
ARDS,
as
, clotting, cultures & urine to
the tra nsfusion. Give
p
178
. Donor should be removed
from donor panel
or
pyretic, eg paracetamol
PLT
S.
If recurrent, use
the tra nsfusion. Give an anti-
WBC
filter
FBC
line open with
)
See p
776
100
% O2. Treat
1
g. Monitor closely.
,
starting transfusion
Urticarial transfusion reaction
Common (1– 3%). Urticaria and itch
Transfusion-associated circulatory
TACO
overload (
Dyspnoea, hypoxia, tachycardia,
)
basal crepitations. No fever
or
10
mg slow IV/ IM. Monitor closely
or
and a diuretic, eg furosemide
JVP
, and
initially. Consider
the transfusion; chlorphenamine
the transfusion. Give oxygen
40
CVP
mg IV
line
345
Blood transfusion and Jehovah’s Witnesses
Adult human beings (with mental ‘capacity’, see p
fuse any medical treatment, even if to do so seems illogical or could result in their
death. To treat patients despite such a refusal would amount to battery under
common law, or could even amount to a degrading act or torture, against which
the European Convention on Human Rights gives absolute, inalienable protection.
The biblical verse ‘no soul of you shall eat blood’ (Leviticus
eral that have been interpreted by some religious groups to extend to acceptance
of blood products in a medical context. Jehovah’s Witnesses, for example, may
refuse potentially vital blood transfusions on such grounds. These views must be
respected, but complex issues arise if the patient is a child, or an adult who may
not be able to give or withhold consent in an informed way. In an immediately
life- threatening situation where further delay may cause harm, treatment such
as blood products may be given in the child’s best interest, but the team should
always involve senior paediatricians and hospital ethicists where practical. If the
requirement is less immediate, then the clinicians should seek further legal advice,
which might involve approaching the Courts.
566
) have an absolute right to re-
17:12
) is one of sev-
8 Haematology
Anticoagulants
LMWH
BNF
UFH
SE
CI
CI
BNF
https://t.me/med1917
346
Main indications (See p
• Therapeutic
• Prophylactic
Venous thromboembolic disease (
Prevention of
Prevention of stroke, eg in chronic
Heparin 1 Low- molecular- weight heparin (
tinzaparin. The preferred option in the prevention and initial treatment of
is also the anticoagulant of choice in malignancy and pregnancy. Inactivates factor
X
a (but not thrombin). t½ is 2- to 4- fold longer than standard heparin, and response
is more predictable: only needs to be given once or twice daily
monitoring is usually not required except in pregnancy, kidney failure, or extremes
of body weight. See
2
Unfractionated heparin (
coagulation is required, eg perioperatively.
nous inhibitor of coagulation), increasing its ability to inhibit thrombin, factor
IX
a. Rapid onset and has a short t½. Monitor and adjust dose with
for both Bleeding (eg at operative site, gastrointestinal, intracranial), heparininduced thrombocytopenia (
osteoporosis are less common with
Bleeding disorders, platelets <50 ×
haemorrhage, severe hypertension, neurosurgery.
someone senior if truly contraindicated in the individual context.
DOAC
s (Direct oral anticoagulants.) Rivaroxaban, apixaban, and edoxaban (factor
X
a inhibitors), and dabigatran (a direct thrombin inhibitor). Generally first- line
agents now as they are at least as eective as warfarin with lower bleeding/ mortality rates, no regular monitoring required, and fewer drug interactions (notable
exceptions include metal valves, valvular
kidney function (apixaban preferable in advanced
kidney function for clearance than other
active bleeding; lesion at risk of bleeding; clotting factors.
Warfarin Used PO OD as long- term anticoagulation. The therapeutic range is
narrow, varying with the condition being treated (see
target levels for
INR
reductase enzyme responsible for regenerating the active form of vitamin
ducing a state analogous to vitamin
severe hypertension, pregnancy (teratogenic, see
elderly and those with past
Beginning therapeutic anticoagulation (Follow local guidelines, and see
treatment of
VTE, LMWH
inhibitors can also be used. When transitioning to a
do not co- administer
combination (as early as day
2
consecutive days (see
on
3
(it takes 48– 72h for anticoagulant eect to develop). Adjust subsequent doses
day
according to the
Antidotes If
fate counteracts heparin: discuss with a haematologist. Warfarin: see
dosage’ and
INR (
UFH/ LMWH
table
8.6
dose, baseline coag/
agement of specific bleeding site,
clonal antibody fragment that binds dabigatran) indicated for dabigatran reversal
if emergency surgery planned, life- threatening or uncontrolled bleeding. Andexanet
alfa, a ‘decoy’ recombinant
FX
a inhibitors in similar circumstances that has not yet been approved in Europe
( thrombotic risk). Consider haemodialysis and prothrombin complex concentrate
PCC
) if idarucizumab and andexanet alfa not available, respectively.
(
573
if need to stop/ hold prior to procedure.)
DVT/ PE
in high- risk patients (p
for doses and for adjustments (accumulates in
) Used where close monitoring of therapeutic anti-
HIT
, see
BOX
), osteoporosis with long- term use.
LMWH
109/ L, previous
VTE)— DVT/ PE, ACS
AF
or prosthetic heart valves.
) Eg dalteparin, enoxaparin,
IV
or SC. Binds antithrombin (an endoge-
than
UFH
. Beware hyperkalaemia.
HIT
.
371
), eg post- op.
VTE. LMWH
SC
, and laboratory
CKD
APTT
(p
340
, peptic ulcer, cerebral
However, always check with
AF
, or
APLS
). Do a bi- annual
CKD
DOAC
’)— and eects are reflected in the
K
deficiency. CI Peptic ulcer, bleeding disorders,
GI
bleeds. Interactions: p
or
UFH
are typically used initially. Treatment doses of FXa
DOAC
and heparin). If transitioning to warfarin, give heparin in
1
) and continue until
BOX
‘Warfarin dosage’). If starting warfarin, check
see table
8.5
).
as it is less dependent on
S).
Severe kidney/ liver impairment;
BOX
INR
OHCS
p
844
741
.
DOAC,
INR
is in target therapeutic range
U&E
to monitor
‘Warfarin guidelines and
. Warfarin inhibits the
). Use with caution in
switch from heparin (ie
overdose: stop infusion. If there is bleeding, protamine sul-
BOX
.
DOAC
S: stop anticoagulant, assess severity and timing of last
FBC/ U&E
, plasma drug levels if available, localization and man-
5
g IV bolus dose idarucizumab (humanized mono-
FX
a molecule, is an
FDA
- approved reversal agent for
‘Warfarin
).
X
a, and
)
.
HIT
K
, pro-
INR
and
.) For
on
8 Haematology
Warfarin guidelines and target levels for
DVT/ PE
https://t.me/med1917
• Pulmonary embolism and
anticoagulated.
• Atrial fibrillation: for stroke prevention (p
• Prosthetic metallic heart valves: for stroke prevention. Target
2.5– 3.5
if m itral va lve.
or
Duration of anticoagulation in
3
months of anticoagulation. Consider extending this to 6 months in patients with
more extensive, life- threatening clot at presentation, for those with transient but
persistent risk factors (eg prolonged immobility) or if evidence of persistent clot at
3
months. For those with recurrent unprovoked emboli or underlying thrombophilia
p
370
), consider bleeding risks against benefits of indefinite treatment.
(
Warfarin dosage and what to do when the
Below is a rough guide to warfarin dosing for target
measured on alternate days until stable, then weekly or less often.
Table 8.
5
Suggested dosing for day 3 of warfarin loading
INR
3
rd dose
Maintenance
*Miss a dose; give
Table 8.
INR
5– 8, no bleed
INR
5– 8, minor bleed*
INR
>8, no bleed
INR
>8, minor bleed* Stop warfarin and admit for urgent IV vitamin K. Check
Any major bleed
(including intracranial
haemorrhage)
* Minor bleeding includes epistaxis.
Vitamin
<
2 2 2.5 2.9 3.3 3.6 4.1
5
mg5mg4mg3mg2mg0.5mg0mg
≥6mg5.5mg4.5mg4mg3.5mg3mg
1– 2
mg the next day; if
6
When the
INR
is much too high (see also
K
may take several hours to work and can cause prolonged resistance
when restarting warfarin, so should be avoided if possible when long- term
anticoagulation is needed. Prothrombin complex concentrate contains a concentrate of factors
of warfarin than
II, VII, IX
FFP.
Heparin- induced thrombocytopenia (
Potentially life- threatening complication resulting from exposure to
Autoantibodies to platelet factor
thrombocytopenia and thrombosis by peripheral platelet consumption and activation, respectively.
female sex.
Management Calculate the 4 Ts (severity of thrombocytopenia, timing of platelet
count drop, presence of thrombosis, and absence of other causes of thrombocytopenia) score to estimate the likelihood of
is a low probability of
not be done, and other causes of thrombocytopenia should be considered (
If the score is >
argatroban, bivalirudin) should be given, and
tients with confirmed
depends on whether or not there has been a thrombotic event.
Risk factors
Presentation Platelets, thrombosis (in 50%; venous > arterial).
HIT
3
, heparin should be stopped, a non- heparin anticoagulant (eg
HIT
DVT
. Aim for
Withhold 1– 2 doses. Restart warfarin at a lower maintenance dose once
Stop warfarin and admit for urgent IV vitamin K (give
slowly). Restart warfarin when
Stop warfarin and seek haematology advice
daily— repeat vitamin K if
warfarin at a lower dose when
Stop warfarin. Give prothrombin complex concentrate 50
units/ kg (if unavailable, give
5– 10
man) and
INR
INR
of 2– 3; 3.5 if recurrent PE or
126
). Target
INR
2– 3.
First episodes of
INR
>4.5, miss 2 doses.
BNF
INR
<
5
mg vitamin
DVT
INR
is much too high
INR
of 2– 3. An
)
INR
<
INR
too high after 24h. Restart
INR
<
5
FFP
15mL/ kg ≈ 1L for a 70kg
K IV
. Discuss with haematologist
DVT
whilst
INR
2– 3 if aortic valve
or PE require at least
INR
needs to be
*
5
INR
, and X and provides a more complete and rapid reversal
HIT
)
LMWH
or
4
complexed with heparin develop and cause
UFH
>
LMWH,
post- op, higher heparin doses,
HIT.
If the score = 0– 3, then there
UFH
— heparin should not be held, antibody testing should
p
343
HIT
antibody should be sent. For pa-
, non- heparin anticoagulation is continued; the duration
347
.
).
8 Haematology
Pancytopenia and bone marrow failure
https://t.me/med1917
348
Bone marrow is responsible for haematopoiesis. In adults, this normally takes
place in the central skeleton (vertebrae, sternum, ribs, skull) and proximal long
bones. In some anaemias (eg thalassaemia), increased demand induces haematopoiesis beyond the marrow (extramedullary haematopoiesis), in liver and spleen,
causing organomegaly. All blood cells arise from an early pluripotent stem cell,
which divides asymmetrically to produce another stem cell and a progenitor cell
committed to a lineage (
myeloid or lymphocyte lineages, releasing their progeny into the blood.
Pancytope nia Reduction in all the major cell lines: red cells, white cells, and plate-
lets. Causes are due to:
(eg acute leukaemia, myelodysplasia, myeloma, lymphoma, solid tumours,
blastic anaemia, myelofibrosis (
Agranulocytosis Implies that granulocytes (
sinophil granules) have stopped being made, leaving the patient at risk of fatal infections. Many drugs can be the culprit: eg carbimazole, procainamide, sulfonamides,
gold, clozapine, dapsone.
warn patients to report any fever. Neutropenia (
initially as a sore throat. Stop the drug, commence neutropenic regimen, & consider
granulocyte colony stimulating factor (
Marrow support Red cells survive for ~
1– 2
d, so early problems are mainly from neutropenia and thrombocytopenia.
1
Red cell transfusion Transfusing 1U should raise Hb by ~10– 15g/ L (p
fusion may drop the platelet count (you may need to give platelets before or after).
2
Platelets Traumatic bleeds, purpura, and easy bruising occur if platelets
50
×
109/ L. Spontaneous bleeding may occur if platelets <20 ×
<
cranial haemorrhage rarely. Platelets are stored at room temperature (
in the fridge). In marrow transplant or if severely immunosuppressed, platelets
may need irradiation before use to prevent transfusion- associated
ABO
must be
20
<
compatible. They are not used in
×
109/ L. • Haemorrhage (eg
opsy, lumbar puncture) to increase count to >
raise the count to >
3
Neutrophils Use neutropenic regimen if the count <0.5 ×
Bone marrow biopsy Gives diagnostic information where there are abnormalities
in the peripheral blood; it is also an important staging test in the lymphoproliferative
disorders. Ideally take an aspirate and trephine usually from the posterior iliac crest
(aspirates can be taken from the anterior iliac crest or sternum). The aspirate provides a film which is examined by microscope. The trephine is a core of bone which
allows assessment of bone marrow cellularity, architecture, and the presence of
infiltrative disease (eg neoplasia). Coagulation disorders may need to be corrected
pre- biopsy. Apply pressure afterwards (lie on that side for
Aplastic anaemia
This is a rare (~5 cases per million/ year) stem cell disorder in which bone marrow
stops making cells, leading to pancytopenia. Presents with features of anaemia
(Hb), infection (
immune, triggered by drugs (eg cytotoxic agents, carbimazole, sulfonamides),
viruses (eg parvovirus, hepatitis), or irradiation. May also be inherited, eg
Fanconi anaemia (
hypocellular). Treatment Mainly supportive in asymptomatic patients. Treat the
WCC
p
underlying cause where possible. Transfuse blood products as required and initiate neutropenic regimen if count <
young patients with severe disease is allogeneic marrow transplantation from an
HLA-
matched sibling, which can be curative. Otherwise, immunosuppression with
ciclosporin and antithymocyte globulin ± eltrombopag may be eective, although
it is not curative in most. Eltrombopag is first line for refractory disease.
fig
8.47
). Committed progenitors further dierentiate into
1
Marrow production Aplastic anaemia (see
p
362
). 2 Peripheral dest ructio n Hyper splen ism.
WBS
S with neutrophil, basophil, or eo-
BOX
), infiltration
TB
), megalo-
When starting drugs known to cause agranulocytosis,
WCC
0.5 ×
109/ L) may declare itself
G- CSF)
if indicated (p
120
d, platelets for ~8d, and neutrophils for
350
).
344
109/ L, with intra-
22
GVHD
ITP
(p
DIC
, p
350
40
×
109/ L in adults; check dose needed with lab.
343
). • Before invasive procedures (eg bi-
50
×
109/ L.
). Indications: • Platelets
4U of platelets should
109/ L (p
1– 2
h if platelets are low).
. Platelets
350
).
), or bleeding (platelets). Causes Most cases are auto-
331
). Tests Bone marrow biopsy is diagnostic (profoundly
0.5
×
109/ L (p
350
). The treatment of choice in
). Trans-
°C; not
8 Haematology
Erythrocyte
NK cell
Megak
Neutrophil
https://t.me/med1917
Reticulocyte
Orthochromatic
erythroblast
Polychromatic
erythroblast
349
Plasma cell
T LymphocyteB Lymphocyte
Basophilic erythroblast
Proerythroblast
Stem cell
Promegakaryocyte
aryocyte
Monocyte
Monocyte
Dendritic cell
Basophil
Fig 8.
47
Haematopoiesis and Sod’s law. When we contemplate a diagram like this (of seemingly
galactic complexity) we, being doctors, think ‘What can go wrong?’ With a sinking feeling we
realize that every arc is an opportunity for multiple disasters. Perhaps, using our own ingenuity,
we might occasionally complete these pathways without Sod intervening (Sod’s law states
that if something can go wrong, it will— here Sod’s tubercular breath is seen blowing the red
cell line o course—
every day each of us makes
we sense that Sod is smiling to himself with especial relish. Anything can go wrong. Everything
can go wrong. This latter we call aplastic anaemia. Agranulocytosis is when the Southerly arcs
go wrong; thrombocytopenia when the West- pointing arcs go wrong. To the East we have the
lymphocytes and their
as for bleeding— how could our predecessors bear to waste a single drop of this stu on purpose?
Our minds are reeling at
there sucient haematinics (eg iron,
Megakaryoblast
Promonocyte
B. promyelocyte E. promyelocyte
TB
is a famous cause of leukoerythroblastic anaemia). When we realize that
B-
and T- cell complexities. Anaemia lies in the North of this diagram. And
175
Myeloid SC
Monoblast
Myeloblast
N. promyelocyte
N. myelocyte
N. metamyelocyte
175
billion red cells, 70 billion granulocytes, and
billion red cells per day— but this is just when the system is idling.
B
, and folate) to allow maximum haemopoiesis?
12
Lymphoid SC
N. band
Prolymphocyte
Lymphoblast
Dendritic cell
Mast cell
Eosinophil
175
billion platelets
Figure © Aria Rad.
8 Haematology
Leukaemia and the on- call junior doctor
DIC
https://t.me/med1917
350
Leukaemia divides into four main types depending on the cell line involved (table
Table 8.
7
Principal subtypes of leukaemia
Lymphoid Myeloid
Acute Acute lymphoblastic leukaemia (
Chronic Chronic lymphocytic leukaemia (
Thes e patients (esp.
ware ne utropenia, see
p
368
) and thus, early involvement of their haematologist is essential. Take non- specific
(
confusion/ drowsiness or just ‘I feel a bit ill today’ seriously: do blood cultures,
U&E, LFT,
Ca
AML
2
+
, glucose, and clotting. Consider
new patient, find out the agreed aim of treatment: cure; prolonging disease- free survival; or palliation with minimal toxicity? Direct your eorts accordingly; get help if
lack of clarity here.
Neutropenic sepsis regimen (For when T° >38°C + neutrophil count ≤0.5 ×
Close liaison with a microbiologist and haematologist is vital. Abide by infection con-
trol procedures! Use a
• Full barr ier nurs ing in a sid e roo m if pos sibl e. H and- washing is vital. Look for infec-
tion (mouth, axillae, perineum, heart, spine,
• Check:
FBC
• Examine oral cavity, dentition, and peri- anal region; fissures, haemorrhoids, skin
, platelets,
Hickman line; urine, sputum, stool if diarrhoea);
CT
abdomen to look for neutropenic enterocolitis (typhlitis) if abdo pain.
excoriation. Oral hygiene (eg hydrogen peroxide mouth washes/
prophylaxis are important (
• Check vital signs 4hrly. High- calorie diet; avoid paracetamol/ antipyretics as they
may mask signs of sepsis. Vases containing flowers pose a Pseudomonas risk.
Use of antibiotics in neutropenia Tr ea t w it hi n 60min of neutropenic fever presen-
T
° >38°C (or T° >37.5°C on two occasions >1h apart) or the patient is septic,
tation. If
start empiric combination therapy according to local guidelines— eg piperacillin–
tazobactam—
aminoglycoside (eg gentamicin) and
p
382
. If signs of severe sepsis/ shock (eg hypotension), add an
the addition of vancomycin, if Gram + ve organisms suspected, eg Hickman line or skin/
soft tissue sepsis. If fever persists despite antibiotics, think of
Aspergillus,
eg co- trimoxazole, though may worsen neutropenia). Remember
p
404
) and central line infection. Consider treatment for Pneumocystis (p
considered— consult haematologist, no survival benefit.
Other dangers •Tumour lysis syndrome Results in K+ , urate, and
• Hyperviscosity (p
368
lung, and heart (leukostasis). Avoid transfusing before lowering
hydroxycarbamide or leukapheresis, as viscosity rises (risk of leukostasis).
•
The release of procoagulants into the circulation causes widespread activation of coagulation, consuming clotting factors and platelets and causing risk of
bleeding. Fibrin strands fill small vessels, haemolysing passing
is also activated.
8.48
) Bruising, bleeding anywhere (eg venepuncture sites),
platelets;
products (
platelets if <
place fibrinogen,
Causes: malignancy, sepsis, trauma, obstetric events. Signs: (fig
PT
;
APTT
D
- dimers). Film: broken
20
×
109/ L (or <50 ×
FFP
use of all- transretinoic acid (
promyelocytic leukaemia (the commonest leukaemia associated with
• Preventing sepsis Give fluoroquinolone (eg ciprofloxacin) before neutropenia gets
serious. Granulocyte colony stimulating factor (
WBC
s (granulocytes) from bone marrow, but should not be given routinely in
of
chemotherapy. Herpes, pneumocystis, and
8.7
ALL
) Acute myeloid leukaemia (
CLL
) Chronic myeloid leukaemia (
AML
CML
)
)
) fall ill suddenly and deteriorate fast, eg with: infection (be-
BOX ‘
Neutropenia’), bleeding (: platelets), and hyperviscosity
CNS
bleeding— CT if in doubt. With any
FBC
109/ L.)5
risk- assessment tool (eg see
INR, U&E, LFT, LDH, CRP
p
242
).
MRSA
BOX ‘ISTH DIC
IVI
site, hard ware ( eg
sco re’).
CVC
)). Take swabs.
. Take cultures (blood ×3— peripherally ±
CXR
if clinically indicated. Consider
2
h) and Candida
coverage (eg vancomycin). Consider also
CMV
, fungi (eg Candida;
396
TB. G- CSF
use can be
AKI
. See p
). If
WCC
is >
100
×
109/ L
WBC
thrombi may form in brain,
RBC
AKI
. Tests: (See
525
WCC
, eg with
S. Fibrinolysis
BOX
; fibrinogen (correlates with severity); fibrin degradation
RBC
S (schistocytes). Treat the cause. Replace
109/ L if serious bleeding), cryoprecipitate to re-
to replace coagulation factors. Heparin is controversial. The
ATRA
) has significantly reduced the risk of
G- CSF
) can increase the production
CMV
prophylaxis has a role.
DIC
DIC
in acute
).
).
,
,
.
.)
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