8
Platelet Low
count
Normal
HAEMATOLOGY
Bleeding Prolonged
time
Prolonged
Normal
APTT Prolonged
Normal
Prolonged
PT Prolonged
Normal
Fig. 8.4  Protocol for investigation of a bleeding disorder
Some will accept the use of Hemopure, a polymerized bovine
haemoglobin.
Transfusions carry the risk of blood-borne viral infections
(Chs. 9 and 21) and circulatory overload.
The platelet count provides a quantitative evaluation of
platelet function. A normal platelet count should be 100 000–
400 000 cells/mm3 (Fig. 8.4). A platelet count of < 100 000
cells/mm3 (thrombocytopenia) can be associated with major
post-operative bleeding. The average lifespan of a platelet ranges
from 7 to 12 days. The bleeding time is occasionally used to
assess adequacy of platelet function. The test measures how long
it takes a standardized skin incision to stop bleeding by the for-
mation of a temporary haemostatic plug. The normal range of
bleeding time depends on the way the test is performed, but is
usually between 1 and 6 min. The bleeding time is prolonged in
patients with platelet abnormalities or taking medications that
affect platelet function.
The activated partial thromboplastin time (APTT) measures
the effectiveness of the intrinsic pathway to mediate fibrin clot
formation. It tests for all factors except for factor VII. The test
is performed by measuring the time it takes to form a clot after
the addition of kaolin, a surface activating factor, and cephalin,
a substitute for platelet factor, to the patient’s plasma. A normal
APTT is usually 25–35 s. APTT is most often used by physi-
cians to monitor heparin therapy.
The prothrombin time (PT) measures the effectiveness of
the extrinsic pathway to mediate fibrin clot formation (Fig.
8.5). It is performed by measuring the time it takes to form
a clot when calcium and tissue factor are added to plasma. A
normal prothrombin time indicates normal levels of factor VII
180 and those factors common to both the intrinsic and extrinsic
Thrombocytopenias
Normal Disorders of platelet function
APTT
von Willebrand disease
Haemophilias, Factor XI
Normal and XII deficiency
PT
Liver disease, anticoagulants,
DIC, others
Factor VII deficiency
Factor XIII deficiency,
drugs, others
pathways (V, X, ­prothrombin, and fibrinogen). A normal pro-
thrombin time is usually between 10 and 15 s. Prothrombin
time is most often used by physicians to monitor oral antico-
agulant therapy such as warfarin. The international normal-
ized ratio (INR) is based on PT and was designed for patients
on chronic anticoagulant therapy. It allows comparisons from
one hospital to another. A patient with normal ­coagulation
parameters has an INR of 1.0. The international normalized
ratio is the prothrombin time (PT) ratio (patient’s PT/con-
trol PT) that would have been obtained if an international
reference thromboplastin reagent had been used and is rec-
ommended by the World Health Organization (WHO) for
reporting PT values. In a person with a PT within the normal
range, the INR is approximately 1. An INR above 1 indicates
that clotting will take longer than normal. An INR of 2–3 is
the usual therapeutic range for deep vein thrombosis, and an
INR of up to 3.5 is required for patients with prosthetic heart
valves.
BLEEDING DISORDERS
GENERAL ASPECTS
Bleeding disorders share common bleeding symptoms, includ-
ing epistaxis and bleeding after surgery or wounds. The latter
are often the first indication of a haemostatic defect. Defects
in haemostasis, leading to bleeding disorders, can comprise
defects in platelet activation and function, contact activation,
the clotting proteins or excess antithrombin function. The
more common causes include: aspirin, one tablet of which
impairs platelet function for almost 1 week (however, this
 8

BLEEDING DISORDERS
Fig. 8.6  Haemarthrosis in an older haemophiliac has caused crippling
arthritis. His five brothers all succumbed to haemophilia at a time when factor
VIII was unknown

Table 8.2  Features of bleeding disorders

Fig. 8.5  Purpura in a patient with myeloid leukaemia

Platelet defects The purpurasa Coagulation defects

Gender affected Females mainly Males

rarely causes ­significant post-operative haemorrhage); warfarin,
Family history Rarely Usually positive
the most common anticoagulant, which interferes with clotting
factor production, via vitamin K blockage; and von Willebrand Nature of bleeding after Immediate Delayed
trauma
disease, the most common inherited bleeding disorder.
Effect when locally May stop bleeding Bleeding recurs
applied pressure removed
CLINICAL FEATURES
Spontaneous bleeding Common Uncommon
Examination may reveal signs of purpura in the skin as in plate- into skin or mucosa, or
from mucosa or gingivae
let disorders (Fig. 8.5). These include leukaemia and human
immunodeficiency virus (HIV) disease. Signs of underlying dis- Bleeding from minor Common Uncommon
ease such as anaemia and lymphadenopathy in leukaemia, for ­superficial injuries
(e.g. needle prick)
example, must also be looked for. Alternatively, purpura may
be localized to the mouth (sometimes grandiloquently termed Deep haemorrhages or Rare Common
‘angina bullosa haemorrhagica’) and not associated with any haemarthroses

abnormal bleeding tendencies. Joint deformities from haemar- Bleeding time Prolonged Normal
throses, characteristic of haemophilia, should also be looked for Tourniquet (Hess) test Positive Negative
but are infrequently seen now (Fig. 8.6).
Platelet count Often low Normal

Clotting function Normal Abnormal

GENERAL MANAGEMENT
Table 8.2 shows comparative features of coagulation defects and
platelet defects. An adequate history is the single most important
part of the evaluation; physical examination is also necessary and
laboratory tests are needed to confirm the diagnosis. An accurate
diagnosis is essential in order to provide replacement therapy
where appropriate, and to enable other management procedures
to be organized. Patients may already be aware of having haem-
orrhagic disease and carry an appropriate medical card.
A history with any suggestion of a haemorrhagic tendency
must be taken seriously. Nevertheless, patients can be remark-
ably capricious as to the information they provide and, in
any case, can hardly be expected to know when bleeding can
legitimately be regarded as ‘abnormal’. Previous dental extrac-
tions provide a useful guide, but prolonged bleeding (up to
24–48 h) as an isolated episode is usually the result of local
aPurpura is rarely vascular.
f­actors, ­especially excessive trauma. By contrast, even patients
who know that they have a serious haemorrhagic tendency can
keep the fact to themselves unless specifically asked.
It should be stressed again that a history of previous haemor-
rhagic episodes is the most important feature since screening
tests of haemostasis do not always detect mild defects.
Special emphasis must be placed on the following, suggestive
of a bleeding disorder:
• deep haemorrhage into muscles, joints or skin – suggests
a clotting defect
• bleeding from and into mucosae – suggests purpura
(Fig. 8.7). 181
 Females often state that they ‘bruise easily’, but any such
8 bruises are usually insignificant and small. Excessive menstrual
bleeding is also rarely due to a bleeding disorder. Most sig-
nificant congenital bleeding disorders become apparent in
childhood and patients may carry a warning card (Fig. 8.8).
HAEMATOLOGY
However, mild haemophiliacs can escape recognition until
adult life if they manage to avoid injury or surgery. A mild
haemophiliac can then have oozing from an extraction socket
for 2–3 weeks despite local measures such as suturing.
Patients who have had tonsillectomy or dental extractions
without trouble are most unlikely to have a severe congenital
bleeding disorder. If previous dental bleeding was controlled by
local measures, the patient is unlikely to have a serious haemor-
rhagic disease. On the other hand, admission to hospital, and
blood transfusion or comparable measures have obvious impli-
cations. Haemorrhagic disease in a blood relative is strongly
suggestive of a clotting defect.
Many drugs such as anticoagulants may cause bleeding ten-
dencies, as may hepatic, renal, HIV and other disease. Some
Fig. 8.7  Oral purpura
A B
182 Fig. 8.8  (A) Special medical card that should be carried at all times by patients with haemorrhagic states; (B) special medical card showing warnings inside the cover
herbal products may impair platelet aggregation and prolong-
ing bleeding (Ch. 26).
Laboratory tests must follow consultation with the haema-
tologist to ensure that they are appropriate. All that is needed
on the request form is to state: ‘History of prolonged bleeding.
Would you please investigate haemostatic function?’ and to give
as much clinical detail as possible. A routine ‘blood count’ will
not identify a clotting defect but may show platelet deficiency.
The sample should be adequately labelled and sent immediately
for testing together with relevant clinical ­information.
Essential tests usually include:
• full blood count, film, platelet count
• prothrombin time (PT) and international normalized
ratio (INR)
• activated partial thromboplastin time (APTT)
• thrombin time (TT) (citrated sample)
• serum for blood grouping and cross-matching.
To exclude platelet defects, a platelet count and full blood
examination are essential, and assays of platelet function may
be indicated. Aspirin should be avoided for at least 7 days
before assessing platelet function. In the Hess test (tourniquet
test), more than a few petechiae appearing on the forearm
when a sphygmomanometer cuff is inflated suggests a platelet
or ­vascular defect, but the test is not particularly sensitive and
is not specific. A bleeding time is not completely reliable. In
vitro tests of platelet adhesion and aggregation may be required
to demonstrate abnormal function. Platelet aggregation can
also be measured using aggregating agents such as ristocetin.
Unfortunately such tests are difficult to standardize and do
not identify all platelet disorders; the clinical features are more
important.
Precise characterization of a congenital clotting defect
depends on assay of the individual factors and a wide range
of other investigations may be indicated according to the type
of case. For example, the assays usually used in diagnosis of
haemophilia A are the APTT and the factor VIII coagulant
(FVIIIC) activity. The whole blood clotting time is uninforma-
tive and obsolete.
It is important also to investigate patients with a suspected
bleeding tendency for anaemia. This is because:
• anaemia is an expected consequence of repeated haemor-
rhages
• any further bleeding as a result of surgery will worsen the
anaemia, or the anaemia may need to be treated before
surgery can be carried out
• anaemia may be an essential concomitant of the haemor-
rhagic tendency – as in leukaemia.
Patients may also need to be screened for liver disease and for
bloodborne infections, particularly HIV and hepatitis viruses.
Patients with bleeding disorders may need to be treated
with replacement of the missing factor. Earlier, use of blood
or blood fractions sometimes resulted in the transmission of
blood-borne viruses and other infections. Recombinant factors
are therefore preferred. In many countries, blood is now col-
lected from donors under careful precautions, and screened to
exclude antibodies to infections such as HIV, hepatitis B, hepa-
titis C, syphilis or cytomegalovirus.
In the developed countries, all cellular blood products are
leukodepleted to limit any possible risk of transmission of pri-
ons and some other infections. Leukocytes in erythrocyte and
platelet concentrates are now considered as a contaminant
since they can cause many other adverse effects, such as the
transmission of other cell-associated infectious agents (e.g.
herpesviruses, prions and Toxoplasma), febrile non-haemolytic
reactions, graft-versus-host disease and immunosuppression.
VASCULAR PURPURA
Vascular purpura rarely causes serious bleeding; any bleeding
into mucous membranes or skin starts immediately after trauma
but stops within 24–48 h.
HEREDITARY HAEMORRHAGIC TELANGIECTASIA
(OSLER–RENDU–WEBER SYNDROME)
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal
dominant condition characterized by telangiectasia on the skin
and mucosae. There may be associated with IgA deficiency or,
rarely, von Willebrand disease (see later).
Clinical features
Telangiectasia on the skin or any part of the oral, nasal, gastro-
intestinal or urogenital mucosa (Fig. 8.9) leads to bleeding and,
consequently, often to iron-deficiency anaemia or, rarely, even
to cardiac failure.
General management
This is by cryosurgery or argon laser treatment if the
­telangiectases have bled significantly or are cosmetically
­unacceptable.
8
BLEEDING DISORDERS
Fig. 8.9  Hereditary haemorrhagic telangiectasia
Dental aspects
Telangiectases may be seen in any part of the mouth and may be
conspicuous on the lips. Bleeding from oral surgery is unlikely
to be troublesome.
Rarely, brain abscesses or other infections have followed oral
procedures that cause bacteraemias but there is no consensus as
to the need for antibacterial prophylaxis.
Regional LA should be avoided because of the risk of deep
bleeding. Conscious sedation can be given if required. In gen-
eral anaesthesia (GA), nasal intubation is best avoided and close
post-operative observation is advisable.
LOCALIZED ORAL PURPURA (‘ANGINA
BULLOSA HAEMORRHAGICA’)
Blood blisters are occasionally seen, typically in older persons,
in the absence of obvious trauma, generalized purpura, any
other bleeding tendency or evidence of any systemic disease.
These blood blisters are often in the palate and may sometimes
be a centimetre or more in diameter and after rupture may
leave a sore area for a few days. When a large blood blister of
this type is in the pharynx, it can cause an alarming choking
sensation and was therefore originally termed ‘angina bullosa
haemorrhagica’. However, almost any site in the mouth can
be affected.
A systemic cause of the blood blisters must be excluded
before the diagnosis of localized oral purpura can be made
confidently and the patient reassured. Other causes of blood
blisters in the mouth include: systemic causes of purpura
such as platelet disorders, amyloidosis (causing factor X
deficiency), leukaemia, infectious mononucleosis, HIV or
rubella; trauma; corticosteroid inhalers; or bleeding into sub-
epithelial blisters such as in mucous membrane pemphigoid
(Ch. 11).
PLATELET DISORDERS
Platelets may be lacking because of failed platelet production
in rare congenital disorders [thrombocytopenia and absent
radii (TAR), Wiskott–Aldrich syndrome, Bernard–Soulier
syndrome, trisomy 13 or 18, thrombocytopenia with Robin 183
 ­syndrome, giant haemangiomas (Kasabach–Merritt syn-

8
Clinical features
drome), type IIb von Willebrand disease]; because of mega-
karyocyte depression (drugs, viruses, chemicals); because Clinical features include petechiae, ecchymoses and post-­
of general bone marrow failure (e.g. alcoholism, cytotoxic operative haemorrhage.
drugs, irradiation, chemicals, drugs, viruses, aplastic anaemia,
HAEMATOLOGY

leukaemia, metastases, megaloblastic anaemia); or because of

excessive platelet destruction (Fig. 8.10). This can be auto-
immune [idiopathic thrombo­cytopenic purpura (ITP) or
HIV] or due to drugs (e.g. aspirin, cytotoxics, beta-lactam
antibiotics and valproate) or diseases (disseminated intravas-
cular coagulation, thrombotic thrombocytopenic purpura,
systemic lupus erythematosus, chronic lymphocytic leu-
kaemia and malaria). Abnormal platelet function is seen in
Glanzmann disease and dysproteinaemias. Abnormal platelet
distribution is seen in splenomegaly or transfusion of stored
blood (Table 8.3).
Platelet numbers or function, if impaired, can cause a bleed-
ing tendency and purpura and changes in results of laboratory
investigations (Table 8.4).
Idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura (ITP), one of the more
common causes of thrombocytopenia, is autoimmune and can
lead to purpura and prolonged bleeding.
General management
Full blood picture and platelet counts are indicated. Cortico-
steroids or other immunosuppressives are the main treatments.
Splenectomy is sometimes needed.
Dental aspects of platelet disorders
The main danger is haemorrhage but it is rarely as severe as
in the clotting disorders. Regional LA block injections can be
given if the platelet levels are above 30 × 109/L. Haemostasis
after dentoalveolar surgery is usually adequate if platelet levels
are above 50 × 109/L. Major surgery requires platelet levels
above 75 × 109/L. Conscious sedation can be given but, if
by the intravenous route, care must be taken not to damage
the vein. GA can be given in hospital but expert intubation
is needed to avoid the risk of submucous bleeding into the
airway.
Platelets can be replaced or supplemented by platelet
transfusions, but sequestration of platelets is very rapid. One

Platelet production Platelet destruction

Bone marrow disease Immunological

(aplastic anaemia, (idiopathic thrombocytopenic
myelodysplastic syndromes, purpura: ITP)
radiotherapy, chemotherapy
drugs, metastatic disease) Pooling in splenomegaly
or haemangiomas
Viral infections
(HIV, CMV, rubella) Coagulation/thrombosis
in disseminated intravascular
Drugs coagulopathy (DIC),
haemolytic–uraemic syndrome
(HUS) or vasculitis

184 Fig. 8.10  Thrombocytopenia

 8
Table 8.3  Platelet defects

Defect Manifestations Management

Thrombasthenia (Glanzmann Defective platelet aggregation due to Severe bleeding tendency Platelet infusions needed pre-

BLEEDING DISORDERS
syndrome) defective membrane protein operatively

Bernard–Soulier syndrome Giant platelets with defect in platelet Heritable disorder resembling von Platelet infusions needed pre-
glycoprotein which acts as receptor for Willebrand disease but considerably operatively
von Willebrand factor more rare

Storage pool deficiency Platelets lack capacity to store serotonin Usually congenital with autosomal Platelet infusion or cryoprecipitate
and adenine nucleotides and inheritance. If associated with corrects the bleeding tendency
consequently fail to aggregate albinism, is termed Hermansky–Pudliak
syndrome

HIV infection Purpura is a relatively common feature of Oral purpura in HIV infection may See Ch. 20
HIV infection. May be autoimmune but closely mimic oral lesions of Kaposi
there appears also to be a platelet sarcoma (Ch. 20)
defect resulting from the infection; drugs
such as zidovudine or some protease
inhibitors and bone marrow disease
may also contribute

Chronic renal failure See Ch. 12

Drugs heparin, dextrans See Ch. 8

Dysproteinaemias See Ch. 8

Myelodysplastic syndrome See Ch. 8

HIV, human immunodeficiency virus.

Table 8.4  Typical findings in platelet disorders

Disorder Bleeding time Platelet count Clot retraction Platelet aggregation Platelet FIII activity

Thrombocytopenia ↑ ↓ ↓ – –

Thrombasthenia ↑ N ↓ ↓ ↓

Storage pool deficiency ↑ N N N or ↓ ↓

Aspirin/von Willebrand disease ↑ N N ↓ (only with ristocetin) N

Thrombocythaemia ↑ ↑ N or ↓ N or ↓ N or ↓

Arrows indicate a value above ↑ or below ↓ normal (N).

FIII, factor III.

unit of platelets should raise the count by around 10 × 109
platelets/L. Platelet transfusions are therefore best used for
controlling already established thrombocytopenic bleeding.
When given prophylactically, platelets should be given – half
just before surgery to control capillary bleeding and half at
the end of the operation to facilitate placement of adequate
sutures. Platelets should be used within 6–24 h after collection
and suitable preparations include platelet-rich plasma (PRP),
which contains about 90% of the platelets from a unit of fresh
blood in about half this volume, and platelet-rich concen-
trate (PRC), which contains about 50% of the platelets from
a unit of fresh whole blood in a volume of only 25 ml. PRC
is thus the best source of platelets. Platelet infusions carry the
risk of isoimmunization, infection with blood-borne agents
and, rarely, graft-versus-host disease. Where there is immune
destruction of platelets (e.g. in ITP), platelet infusions are less
effective.
The need for platelet transfusions can be reduced by local
haemostatic measures and use of desmopressin or tranexamic
acid or topical administration of platelet concentrates. Absorb-
able haemostatic agents such as oxidized regenerated cellulose
(Surgicel), synthetic collagen (Instat) or microcrystalline col-
lagen (Avitene) may be put in the socket to assist clotting.
Splenectomy predisposes to infections, typically with pneu-
mococci, and especially within the first 2 years. Systemic infec-
tion post-splenectomy, involving oral streptococci, is rare and
antimicrobial prophylaxis is not therefore generally recom-
mended before invasive dental procedures.
Long-term corticosteroids can cause well-recognized prob-
lems (Ch. 6). Drugs such as aspirin and other non-steroidal
­anti-inflammatory drugs (NSAIDs) which damage platelets
should be avoided (Table 8.5). Aspirin’s effects are not dose
dependent: even a single tablet can affect platelet cyclo-­
oxygenase (COX) irreversibly for about a week. Other NSAIDs 185
 may have a reversible effect and act for only up to 48 h. COX-2

8
Table 8.5  Some drugs that may impair platelets or their
function inhibitors have no such effect on platelets.
Perioperative management is summarized in Table 8.6. Sub-
Class Examples mucous purpura may be conspicuous and sometimes seen as
‘blackcurrant jelly’ blood blisters.
HAEMATOLOGY

Alcohol

Antibiotics Amoxicillin
Ampicillin and derivatives Thrombocytosis
Azithromycin
Carbenicillin A raised platelet count (thrombocytosis) may be found in many
Cephalosporins conditions, and predisposes to arterial thrombosis.
Gentamicin
Methicillin
Penicillin G (benzyl penicillin) COAGULATION DEFECTS
Rifampicin
Sulfonamides Coagulation defects are due mainly to genetic defects of clot-
Trimethoprim ting factors (von Willebrand disease and haemophilia), to anti-
Analgesics and other platelet Aspirin and other NSAIDs
coagulant therapy or to a range of diseases, especially liver or
inhibitors Clopidogrel kidney diseases (Box 8.1).
Clotting disorders cause a range of changes in results of labo-
Cytotoxic drugs Many
ratory investigations (Table 8.7).
General anaesthetic agents Halothane

Psychoactive drugs Antihistamines (some)

Congenital coagulation defects
Chlorpromazine
Diazepam The most important hereditary bleeding disorder in terms of
Haloperidol
prevalence and severity is von Willebrand disease, but hae-
Tricyclic antidepressants
Valproate mophilia A and B are the other most common coagulopa-
thies. Haemophilia A and B (Christmas disease) are hereditary
Diuretics Acetazolamide
Chlorothiazide
X-linked recessive disorders characterized by deficiencies in
Furosemide blood clotting factors VIII and IX, respectively. Factor XI defi-
ciency is also important. Less common disorders are summa-
Antidiabetics Tolbutamide
rized in Table 8.8 and Appendix 8.1.
Cardiovascular drugs Digitoxin
Quinine Haemophilia A
Oxprenolol
Heparin Haemophilia
Methyldopa Haemophilia A affects approximately 1 in 5000 males. Carriers
of haemophilia rarely manifest a bleeding tendency clinically.
NSAIDs, non-steroidal anti-inflammatory drugs.

Table 8.6  Thrombocytopenia manifestations and management of surgery

MANAGEMENT IN RELATION TO TYPE OF ORAL SURGERY

Platelet count Severity of
(× 109/L) thrombocytopenia Manifestations Dentoalveolar Maxillofacial

100–150 Mild Mild purpura ­sometimes. No platelet transfusion. Local haemostatic Consider platelet transfusion. Local
Slightly prolonged measures.a Observe haemostatic measures.a Observe
­post-operative bleeding

50–100 Moderate Purpura, post-operative Platelets may be needed. Local haemo- Platelets needed. Local haemostatic
bleeding static measures.a Consider post-operative measures.a Post-operative tranexamic
tranexamic acid mouthwash for 3 days acid mouthwash for 3 days

30–50 Severe Purpura, post-operative Platelets needed. Local haemostatic Platelets needed. Local haemostatic
bleeding, even from measures.a Post-operative tranexamic acid measures.a Avoid surgery where
­venepuncture mouthwash for 3 days ­possible. Post-operative tranexamic
acid mouthwash for 3 days

< 30 Life-threatening Purpura, spontaneous Platelets needed. Local haemostatic Platelets needed. Local haemostatic
bleeding measures.a Avoid surgery where possible. measures.a Avoid surgery where
Post-operative tranexamic acid mouthwash ­possible. Post-operative tranexamic
for 3 days acid mouthwash for 3 days

186 aLocal haemostatic measures = compressive packing, sutures, and microfibrillar collagen or oxidized cellulose.
 8
Box 8.1  Main coagulation defects Table 8.8  Coagulation factor defects: in descending order of
frequency
• Anticoagulants and thrombolytic agents
• Chronic renal failure
Factor deficient Inheritance Incidence. 1 in
• Deficiencies of factors XII and XIII and others

BLEEDING DISORDERS
• Disseminated intravascular coagulation VIII X-linked 10 000
• Dysproteinaemias, especially multiple myeloma
• Haemophilia IX X-linked 60 000
• Liver disease, including obstructive jaundice
VII Autosomal recessive 500 000
• Lupus erythematosus
• Von Willebrand disease V Autosomal recessive 1 million

X Autosomal recessive 1 million

XI Autosomal recessive 1 million

XIII Autosomal recessive 1 million

Table 8.7  Laboratory findings in clotting disorders
Fibrinogen Autosomal recessive 1 million
Disorder PT APTT TT FL FDP Prothrombin Autosomal recessive 2 million

Haemophilia A; haemophilia B; N ↑ N N N
von Willebrand disease; defi-
ciency of factors XI and XII neck, can be fatal. Abdominal haemorrhage may simulate an
Warfarin or other coumarin ther- ↑ ↑ N N N ‘acute abdomen’. Haemarthroses can cause joint damage and
apy; obstructive jaundice, or other cripple the patient.
causes of vitamin K deficiency; Abnormal bleeding after extractions has sometimes led to
deficiency of factor V or X recognition of haemophilia. Dental extractions lead to pro-
Heparin therapy; disseminated ↑ ↑ N N N longed bleeding and, in the past, have been fatal.
intravascular coagulation The severity of bleeding in haemophilia A correlates with the
Parenchymal liver disease ↑ ↑ ↑ ↓ ↑ level of factor VIII:coagulant (VIII:C) activity and degree of
trauma (Table 8.9). Normal plasma contains 1 unit of factor
Deficiency of factor VII ↑ N N N N
VIII per millilitre, a level defined as 100%.
APTT, activated partial thromboplastin time (or KPTT); FDP, fibrin degradation
products; FL, fibrinogen level; PT, prothrombin time; TT, thrombin time.
Arrows indicate a value above ↑ or below ↓ normal (N).
Risk of potentially
Risk of fatal cranial bleeding
potential fatal
bleeding
General aspects around airway Persistent bleeding after
dental extractions
Haemophilia A is an X-linked disorder resulting from a defi- Spontaneous gingival
ciency in blood clotting factor VIII, a key component of the bleeding
coagulation cascade.
Haemophilia A affects males. Sons of carriers have a 50:50
chance of developing haemophilia while daughters of carri-
ers have a 50:50 chance of being carriers. All daughters of an
affected male are carriers but sons are normal. Carriers rarely
Abdominal bleeding
have a clinically manifest bleeding tendency.
Haemophilia A, with a prevalence of about 5 per 100 000 of
the population, is about ten times as common as haemophilia
B except in some Asians, where frequencies are almost equal.
Haemophilia A arises from a variety of mutations: some 150
different point mutations have been characterized. A family his-
tory can be obtained in only about 65% of cases.

Clinical features Haemarthroses/joint

Haemophilia is characterized by excessive bleeding, particu- bleeding and deformity
larly after trauma and sometimes spontaneously. Haemorrhage
appears to stop immediately after the injury (due to normal vas-
cular and platelet haemostatic responses) but intractable oozing
with rapid blood loss soon follows. Haemorrhage is dangerous
either because of acute blood loss or due to bleeding into ­tissues,
particularly the brain, larynx, pharynx, joints and muscles
(Fig. 8.11). Bleeding into the cranium, or compression of the
larynx and pharynx following haematoma formation in the Fig. 8.11  Haemophilia 187
 General management
8
The diagnosis of haemophilias is based upon the clinical
­presentation, a positive family history, coagulation studies and
clotting factor assays. Typical findings are shown in Box 8.2.
Haemophiliacs should be under the care of recognized hae-
HAEMATOLOGY
mophilia reference centres. Factors VIII or IX must be replaced
to adequate levels during episodes of bleeding and ascertained
pre-operatively. Synthetic vasopressin (DDAVP) acts to increase
factor VIII levels and may be used in very mild haemophilia.
‘Gene therapy’ and ‘gene-delivery systems’ raise the possibility
of a potential cure for haemophilia in the future.
Rarely, von Willebrand disease may mimic haemophilia, and
though the history may help to distinguish them, laboratory
testing is essential (see later).
Factor VIII must be replaced to a level adequate to ensure
haemostasis if bleeding starts or is expected. In mild haemo-
philia, desmopressin and antifibrinolytics such as tranexamic
acid may be adequate (see later).
Replacement of the missing clotting factor is achieved with
porcine factor VIII or recombinant factor VIII. Plasma (fresh
or frozen), cryoprecipitate or fractionated human factor con-
centrates obtained from pooled blood sources have had, and
may still occasionally have, the potential to carry blood-
borne pathogens. Regular prophylactic replacement of factor
VIII is used when possible but necessitates daily injections as
the half-life is around 12 h, and its use may be complicated by
antibody formation. Desmopressin (deamino-8-d-arginine
vasopressin; DDAVP) is a synthetic analogue of vasopres-
sin that induces the release of factor VIIIC, von Willebrand
factor and tissue plasminogen activator from storage sites in
endothelium. Desmopressin cover just before surgery, and
repeated 12-hourly if necessary for up to 4 days, is useful
to cover minor surgery in some very mild haemophiliacs,
but factor VIII cover may be needed if there is any doubt
about haemostasis. Desmopressin can be given as an intra-
nasal spray of 1.5 mg desmopressin per ml with each 0.1 ml
pump spray, or as a slow intravenous infusion over 20 min of
0.3– 0.5 μg/kg.
Tranexamic acid (Cyklokapron) is a synthetic derivative
of the amino acid lysine. It exerts an antifibrinolytic effect
through the reversible blockade of lysine binding sites on
plasminogen molecules. Tranexamic acid significantly reduces
blood loss after surgery in patients with haemophilia and can
be used topically or systemically. Systemically, it is given in
a dose of 1 g (30 mg/kg) orally, four times daily starting at
least 1 h pre-operatively for surgical procedures, or as infusion
10 mg/kg in 20 ml normal saline over 20 min, then 1 g orally
three times daily for 5 days (child’s dose is 20 mg/kg). How-
ever, nausea is a common adverse effect and antifibrinolytics
must not be used systemically where residual clots are present
(e.g. in the urinary tract or intracranially). Tranexamic acid
is not approved for use in the USA by the Food and Drug
Administration (FDA), where epsilon-aminocaproic acid is an
alternative.
Dental aspects
Many of the coagulation defects present a hazard to surgery
and to LA injections, but in general the teeth erupt and exfo-
188 liate without problems, and non-invasive dental care is safe.
Table 8.9  Severity of haemophilia
% factor VIII Clinical features
Severe <1 Spontaneous bleeding, typically from
childhood with bleeding into muscles or
joints (haemarthroses), easy bruising and
prolonged bleeding from minor injuries
Moderate 1–5 Comparatively minor trauma may still lead
to significant blood loss
Mild > 5–25 Comparatively minor trauma may still lead
to significant blood loss. Bleeding after
dental extractions is sometimes the first or
only sign of mild disease
Very mild > 25 Patient can generally lead a normal life
and may remain undiagnosed but there
can be prolonged bleeding after trauma or
surgery. Some may not bleed excessively
even after a simple dental extraction, so
that the absence of post-extraction haemor-
rhage cannot reliably be used to exclude
haemophilia. Most will, however, bleed
excessively after more traumatic surgery,
such as tonsillectomy
Box 8.2  Laboratory findings in haemophilias
• Normal prothrombin time (and INR)
• Normal bleeding time
• Prolonged activated partial thromboplastin time
• Reduced factor VIII:C level (haemophilia A)
• Reduced factor IX level (haemophilia B)
• Normal levels of von Willebrand factor
Close cooperation is needed between the physician and dentist
to plan safe, comprehensive dental care.
Haemophiliacs form a priority group to minimize the need
for dental operative intervention, which can cause severe, or
occasionally fatal, complications. Education of patients or
­parents, and preventive dentistry, should be started as early as
possible in the young child, when the teeth begin to erupt. Car-
ies must be minimized or avoided. The use of fluorides, fissure
sealants, dietary advice on the need for sugar restriction and
regular dental inspections from an early age are crucial to the
preservation of teeth. Prevention of periodontal disease is also
imperative. Comprehensive dental assessment is needed at the
age of about 12–13, to plan to decide how best to forestall diffi-
culties resulting from overcrowding, or misplaced third molars
or other teeth.
Local anaesthesia injections or surgery can be followed by
persistent bleeding for days or weeks, the haemorrhage cannot
be controlled by pressure alone and the problem may be life-
threatening. Management of haemophiliacs should take consid-
eration of the factors listed in Box 8.3.
The bleeding tendency can be aggravated by NSAIDs. It may
also be aggravated by other factors such as liver damage after
hepatitis, in HIV disease, by thrombocytopenia and the effects
of drugs such as protease inhibitors. Paracetamol, codeine and
COX-2 inhibitors are safer.

Box 8.3  Factors to consider in haemophilia management
• Aggravation of bleeding by drugs
• Anxiety
• Dental neglect necessitating frequent dental extractions
• Drug dependence as a result of chronic pain
• Factor VIII inhibitors
• Hazards of anaesthesia, nasal intubation and intramuscular injections
• Hepatitis and liver disease
• Human immunodeficiency virus infection
• Trauma, surgery and subsequent haemorrhage
Local anaesthesia regional blocks, lingual infiltrations or
injections into the floor of the mouth must not be used in
the absence of factor VIII replacement because of the risk of
­haemorrhage hazarding the airway and being life-threatening.
Rarely, even submucosal LA infiltrations have caused widespread
haematoma formation. If factor VIII replacement therapy has
been given, regional LA can be used, providing the factor VIII
level is maintained above 30%, but infiltration LA is still prefer-
able. Lingual infiltration should be avoided. Intraligamentary
LA injections are safer.
Intramuscular injections of drugs should be avoided unless
replacement therapy is being given, as they can cause large hae-
matomas. Oral alternatives are, in any case, usually satisfactory.
In all but severe haemophiliacs, non-surgical dental treat-
ment (taking into consideration the question of LA discussed
above) can usually be carried out under antifibrinolytic cover
(usually tranexamic acid).
Conservative dentistry treatment of the primary dentition
may be carried out without LA. If conservative treatment in
the permanent dentition is not feasible without LA, papillary or
intraligamentary infiltration is unlikely to cause serious bleed-
ing. Alternative techniques such as electronic dental anaesthesia
may be also effective. Soft tissue trauma must be avoided and
a matrix band may help prevent gingival laceration. However,
care must be taken not to let the matrix band cut the peri-
odontal tissues and start gingival bleeding. A rubber dam is
also useful to protect the mucosa from trauma but the clamp
must be carefully applied. Cotton rolls may cause mucosal
bleeding unless they are wetted before removal. High-speed
vacuum aspirators and saliva ejectors can cause haematomas.
Trauma from the saliva ejector can be minimized by resting it
on a gauze swab in the floor of the mouth.
Endodontic treatment may obviate the need for extractions
and can usually be carried out without special precautions other
than care to avoid instrumenting through the tooth apex. The
use of an electronic endometric instrument will reduce the
number of intraoperative radiographs. Topical application of
10% cocaine to the exposed pulp is recommended for vital pulp
extirpation. Intracanal injection of LA solution containing epi-
nephrine or topical application (with paper points) of epineph-
rine 1:1000 may be useful to minimize bleeding. However, in
severe haemophilia, bleeding from the pulp and periapical tis-
sues can be persistent and troublesome.
Periodontal surgery necessitates LA and factor VIII replace-
ment to a level of 50–75%. In all but severe haemophiliacs,
scaling can be carried out under antifibrinolytic cover. Minor
procedures may be carried out with topical anaesthesia.
8
Table 8.10  Topical haemostatic agents
Agent Main constituent Source
Avitene Collagen Bovine
BLEEDING DISORDERS
Beriplast Fibrin Various
Colla-Cote Collagen Bovine
Cyclokapron Tranexamic acid Synthetic
Gelfoam Gelatin Bovine
Helistat Collagen Bovine
Instat Collagen Bovine
Surgicel Cellulose Synthetic
Thrombinar Thrombin Bovine
Thrombogen Thrombin Bovine
Thrombostat Thrombin Bovine
Orthodontics: there is no contraindication to the movement
of teeth in haemophilia. However, there must be no sharp edges
to appliances, wires, etc., which might traumatize the mucosa.
Extractions and dentoalveolar surgery should be carefully
planned. Ideally all necessary surgery (and other dental treat-
ment) should be performed at one operation. A factor VIII
level of 50–75% is required. Panoramic radiographs should be
taken for any unsuspected lesion and to assess whether further
extractions might prevent future trouble. LA should be given as
discussed above. Local measures are important to minimize the
risk of post-operative bleeding. Surgery should be carried out
with minimal trauma to both bone and soft tissues, and careful
mouth toilet post-operatively is essential. Suturing is desirable
to stabilize gum flaps and to prevent post-operative disturbance
of wounds by eating. A non-traumatic needle must be used,
and the number of sutures minimized. Vicryl sutures are pre-
ferred and catgut is best avoided. Non-resorbable sutures such
as black silk should be removed at 4–7 days. Suturing carries
with it the risk, if there is post-operative bleeding, of causing
blood to track down towards the mediastinum with danger to
the airway due to inadequate pre-operative replacement ther-
apy or factor VIII inhibitors being present.
In the case of difficult extractions, when mucoperiosteal flaps
must be raised, the lingual tissues in the lower molar regions
should preferably be left undisturbed since trauma may open
up planes into which haemorrhage can track and endanger
the airway. The buccal approach to lower third molars is safer.
Minimal bone should be removed and teeth should be sec-
tioned for removal where possible. Acrylic protective splints
are now rarely used, in view of their liability to cause mucosal
trauma and to promote sepsis, but they are sometimes useful
in sites such as the palate. The packing of extraction sockets
is unnecessary if replacement therapy has been adequate but a
little oxidized cellulose soaked in tranexamic acid placed into
the base of the sockets, or collagen, or cyanoacrylate or fibrin
glues (Table 8.10) may be used. Fibrin sealant, which consists
mainly of fibrinogen and thrombin, provides rapid haemostasis
as well as tissue sealing and adhesion. Liquid fibrin sealant has
been used but fibrin glue is unavailable in USA, because of the 189
 risk of viral infections: recombinant fibrin glues are becoming
8 available. Local use of fibrin glue and swish and swallow rinses
of tranexamic acid before and after the dental extractions is a
cost-effective regimen.
Post-operatively, a diet of cold liquid and minced solids should
HAEMATOLOGY
be taken for up to 5–10 days. Care should be taken to watch
for haematoma formation which may manifest itself by swell-
ing, dysphagia or hoarseness. The patency of the airway must
always be ensured. Infection also appears to induce fibrinolysis,
so antimicrobials such as oral penicillin V 250 mg or amoxicillin
500 mg four times daily should be given post-operatively for
a full course of 7 days to reduce the risk of ­secondary haem-
orrhage. Antibiotic prophylaxis may be indicated for patients
with prosthetic joints (Ch. 16). In HIV-infected patients, mild
cytopenias are common but severe anaemia, neutropenia and
thrombocytopenia that predispose to oral manifestations and
surgical complications are rare and post-operative bleeding is
uncommon in HIV-infected haemophiliacs.
After trauma to the head and neck in haemophiliacs, factor
VIII replacement is essential because of the risk from bleeding
into the cranial cavity or into the fascial spaces of the neck. Hae-
mophiliacs should, therefore, be given factor VIII to achieve
a level of 100% prophylactically after head or facial trauma. If
there are lacerations that need suturing, a minimum level of fac-
tor VIII of 50% is required at the time, with further cover for
3 days (see Table 8.11).
Haemophiliacs with inhibitors
The haematologist must always be consulted. Factor VIII
inhibitor levels should be checked pre-operatively and, in gen-
eral, patients with low-titre inhibitors can have dental treatment
in the same way as those who have no antibodies.
Those with high-titre inhibitors need special care. In the
latter group, traumatic procedures must be avoided unless
absolutely essential. Human factor VIII inhibitor bypassing
fractions (FEIBA) can often be effective; these are usually either
non-activated prothrombin complex concentrates (PCC) or
activated prothrombin complex concentrates (APCC), which
act by activating factor X, directly bypassing the intrinsic path-
way of blood clotting. The danger with these products is of
Table 8.11  Outline of management of haemophiliacs requiring surgery
Operation Factor VIII level required
Dental extraction, Minimum of 50% at operation
­ entoalveolar or
d Tranexamic acid 1 g i.v. (or by
periodontal surgery
Maxillofacial surgery 75–100% at operation; at least
50% for 7 days post-operatively
aFactor VIII dose in units = weight in kilograms × 25 given 1 h pre-operatively.
bFactor VIII dose in units = weight in kilograms × 50 given 1 h pre-operatively.
190 cLocal haemostatic measures (see Table 8.10).
uncontrolled coagulation with thromboses. The real choice
lies between either prothrombin-complex concentrates (e.g.
FEIBA), or recombinant factor VIIa. In some cases, desmo-
pressin is an effective alternative, and antifibrinolytics may help.
Conscious sedation can be given but, if intravenous, great
care must be taken to avoid damaging the vein. If GA is needed,
nasal intubation should be avoided.
Haemophilia B
General and clinical aspects
Haemophilia B (Christmas disease; factor IX deficiency) is clini-
cally identical to haemophilia A and inherited in the same way,
but is about one-tenth as common as haemophilia A except in
some Asians, where frequencies are almost equal. Female carri-
ers of haemophilia B (unlike haemophilia A) often have a mild
bleeding tendency.
General management
Replacement therapy is with synthetic factor IX, which is more
stable than factor VIII with a half-life of 18 h but often up to
2 days, so that replacement therapy can sometimes be given at
longer intervals than in haemophilia A. A dose of 20 units of
factor IX per kilogram body weight is given intravenously 1 h
pre-operatively.
Dental aspects
Comments on dental management in haemophilia A apply to
patients with haemophilia B, apart from using factor IX, and
not using desmopressin.
Von Willebrand disease
General aspects
Von Willebrand disease (vWD; pseudohaemophilia) is the most
common inherited bleeding disorder and is due to a deficiency
of von Willebrand factor (vWF). This is synthesized in endo-
thelium and megakaryocytes, mediates platelet adhesion to
damaged endothelium and protects factor VIII from proteo-
lytic degradation. Von Willebrand factor has binding sites for
collagen and for platelet glycoprotein (GP) receptors, and thus
normally acts in three ways. vWF normally binds to GP Ib and
Pre-operatively give Post-operative schedule
Factor VIII i.v.a Local haemostatic measuresc
mouth starting 24 h pre-operatively)
Factor VIII i.v.b Local haemostatic measuresc
Rest as inpatient for 7 days unless resident close to
centre (then 3 days)
Soft diet. For 10 days give tranexamic acid 1 g qid
and pencillin V 250 mg qid
If there is bleeding during this period, give repeat
dose of factor VIIIa
Rest inpatient for 10 days
Soft diet. Twice daily i.v. factor VIIIa for 7–10 days
 8
Table 8.12  Types of von Willebrand disease (vWD)

Type % vWD Defect in von Willebrand factor (vWF) Factor VIIIC Features

1 80 Partial lack May be normal Autosomal dominant inheritance. Disease is mild

BLEEDING DISORDERS
and is characterized by bleeding from mucous
2A 15 Partial lack but impaired function Low
­membranes – nose bleeds, gingival haemorrhage
2B Rare Partial lack but impaired function Low and gastrointestinal blood loss

2M Rare Partial lack but impaired function Low

2N Rare Partial lack but impaired function Low

3 5 Complete lack Low Bleeding is more severe than in types 1 and 2 but joint
and muscle bleeds characteristic of haemophilia are rare

Local haemostatic measures (as Table 8.10 + tranexamic acid mouthwash).

acts as a carrier for factor VIII protecting it from proteolytic

Table 8.13  Haemophilia A and von Willebrand disease
degradation. Thus a deficiency leads also to a low factor VIII
concentration in the blood. vWF also mediates platelet adhe- Von Willebrand
sion to damaged endothelium. vWF mediates platelet aggre- Haemophilia A disease
gation. Thus a deficiency leads to defective platelet adhesion
Inheritance dominant Sex-linked recessive Autosomal
which causes a secondary deficiency in factor VIII. Clinically
significant vWD affects approximately 1% of the population and Haemarthroses/deep Common Rare
haematomas
6% of women with menorrhagia. This is a frequency at least
twice that of haemophilia A. Rarely, vWD may be acquired, Epistaxes Uncommon Common
particularly in patients with autoimmune or lymphoprolifera- Gastrointestinal bleeding Uncommon Common
tive diseases.
Haematuria Common Uncommon
Von Willebrand disease affects females as well as males and
usually has an autosomal dominant inheritance, but a severe Menorrhagia None (males) Common

form of the disease may be inherited as a sex-linked recessive Post-extraction ­bleeding Starts 1–24 h after Starts immediately,
trait like true haemophilia. trauma, lasts 3–40 lasts 24–48 h and
days and is not con- is often controlled
trolled by pressure by pressure
Clinical features
The types of von Willebrand disease are shown in Table 8.12. Bleeding time Normal Prolonged

Von Willebrand disease causes bleeding that has features
similar to those caused by platelet dysfunction, but if severe it
can resemble haemophilia (Table 8.13). The common pattern
is bleeding from, and purpura of, mucous membranes and the
skin. Gingival haemorrhage is more common than in haemo-
philia. Post-operative haemorrhage can be troublesome: exces-
sive haemorrhage may occur after dental treatment and surgery.
Excessive menstrual bleeding is common in females. Haem-
arthroses are possible but are rare.
The severity also varies from patient to patient and from time
to time. Some patients have a clinically insignificant disorder,
while others have factor VIII levels low enough to cause severe
clotting defects as well as a prolonged bleeding time. How-
ever, the severity does not correlate well with the factor VIII
level. Pregnancy and the contraceptive pill may cause transient
­amelioration.
Rarely, hereditary haemorrhagic telangiectasia, IgA deficiency,
mitral valve prolapse or factor XII deficiency may be associated.
General management
Von Willebrand disease is characterized by the laboratory find-
ings shown in Box 8.4.
Before surgery, patients with vWD need treatment to reduce
the risk of haemorrhage, which may include the administration
of factor VIII concentrate and synthetic vasopressin (DDAVP)
(Table 8.14).
Factor VIII coagulant Low Low
activity
Factor VIIIR:RCo (plasma Normal Low
factor VIII complex;
­ristocetin cofactor)
Note: severe von Willebrand disease is occasionally identical to ­haemophilia.
Box 8.4  Laboratory findings in von Willebrand disease
• Prolonged bleeding time
• Prolonged activated partial thromboplastin time
• Low levels of von Willebrand factor (factor VIIIR:Ag).
• Low factor VIIIC levels
• Reduced platelet aggregation in the presence of ristocetin
Dental aspects
Desmopressin (DDAVP) is invariably effective in type 1 vWD
and is usually given by either intravenous infusion or subcuta-
neous injection although a nasal spray is also available. DDAVP
may be effective in type 2A and it is often helpful to give
patients a trial dose to ascertain the response.
Desmopressin (DDAVP) is contraindicated in type 2B vWD
because it stimulates release of dysfunctional vWF, which leads in
turn to platelet aggregation and severe but transient thrombo-
cytopenia. Clotting factor replacement is needed. ­Intermediate 191
 purity factor VIII, cryoprecipitate and fresh-­frozen plasma are

8
Factor XIII deficiency
effective though pure factor VIII may be ineffective replace-
ment. DDAVP is contraindicated in type 3 vWD where so little Factor XIII, the pro-enzyme of plasma transglutaminase, is
vWF is formed that essentially the same management is required normally activated by thrombin in the presence of calcium to
as for haemophilia, a. Clotting factor replacement is needed. catalyse the cross-linking of fibrin monomers.
HAEMATOLOGY

In all types, aspirin and NSAIDs should be avoided. Infil-
tration or intraligamentary LA should generally be used. Con-
scious sedation can be given, but care must be taken not to
damage the vein. GA must be given in hospital where expert
attention is available. Intubation is a possible hazard because of
the risk of submucosal bleeding in the airway.
Factor XIII deficiency leads to neonatal umbilical cord
bleeding, intracranial haemorrhage and soft tissue haemato-
mas. ­Primary haemostasis is normal but delayed bleeding is
seen.
Fibrinogen disorders

Inherited disorders in fibrinogen are rare (Table 8.15). In

Factor XI deficiency (‘haemophilia C’)
Common in Ashkenazi Jews, factor XI deficiency is inherited as
an autosomal disorder with either homozygosity or compound
heterozygosity.
Patients with factor XI deficiency cannot activate ­thrombin-
activatable fibrinolytic inhibitor TAFI; this results in rapid fibri-
nolysis, which is responsible for the bleeding tendency seen in
this disorder. Fresh-frozen plasma or ­factor XI is required.
Factor XII deficiency
Factor XII (the first component of the intrinsic pathway) is
more important for the generation of bradykinin and stimula-
tion of fibrinolysis than for initiation of coagulation. Patients
with factor XII deficiency rarely show signs of haemorrhage.
Table 8.14  Von Willebrand disease: cover for operationsa
contrast, raised plasma fibrinogen levels are found in coronary
artery disease, diabetes, hypertension, peripheral artery ­disease,
hyperlipoproteinaemia, hypertriglyceridaemia, pregnancy,
menopause, hypercholesterolaemia, use of oral contraceptives
and smoking.
Acquired coagulation defects
Acquired haemorrhagic disorders are far more prevalent than
congenital diseases but, except in anticoagulant therapy or
liver disease, are usually less severe. Important causes include
­anticoagulant therapy and liver disease, vitamin K deficiency or
malabsorption, disseminated intravascular coagulation, fibri-
nolytic states, amyloidosis (deficiency of factor X) and auto­
immune disorders (e.g. acquired haemophilia). Some patients
also have clinical bleeding tendencies but no defect detectable
by current laboratory methods.

Von Willebrand Factor VIII ANTICOAGULANT TREATMENT

disease type Desmopressin replacement
GENERAL ASPECTS
1 Typically effective –
Anticoagulants are given to prevent and treat thromboembolic
2A May be effective: check ± disease but have many uses. They are used to treat atrial fibrilla-
response with trial dose
tion, cardiac valvular disease, ischaemic heart disease and post-
2B Contraindicated + myocardial infarction (sometimes), deep venous thrombosis
2M Contraindicated + (DVT), pulmonary embolism, cerebrovascular accident and
many other conditions, and are used when there are heart valve
2N Unlikely to be of value ±
replacements or renal dialysis.
3 Contraindicated + Commonly used anticoagulants are the coumarin warfarin
aPlus local haemostatic measures (Table 8.10). for long-term treatment and heparin for short-term treatment.

Table 8.15  Inherited disorders in fibrinogen

Condition Definition Inheritance Features

Afibrinogenaemia Complete lack of fibrinogen Autosomal recessive Neonatal umbilical cord haemorrhage, ecchymoses,
mucosal haemorrhage, internal haemorrhage and
recurrent abortion

Hypofibrinogenaemia Low levels of fibrinogen below Acquired or inherited Symptoms similar to but less severe than
100 mg/dl (normal – 250–350 mg/dl) afibrinogenaemia

Dysfibrinogenaemia Dysfunctional fibrinogen Inherited Haemorrhage, spontaneous abortion and thrombo­

embolism

Hypoplasminogenaemia Plasminogen deficient or defective Inherited Fibrin deposits with gingival swelling and sometimes
ligneous conjunctivitis
192