STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

TABLE OF CONTENTS

GOALS AND OBJECTIVES.......................................................................................................... 2

INTRODUCTION ........................................................................................................................ 3

TOPIC 1: DISORDERS OF THE BLOOD CELLS.......................................................................... 5

1.1. Anaemia ............................................................................................................. 5
1.2. Polycythaemia..................................................................................................... 5
1.3. Neutropenia......................................................................................................... 5
1.4. Neutrophilia ......................................................................................................... 6
1.5. Thrombocytopenia................................................................................................ 6
1.6. Thrombocytosis ................................................................................................... 6

TOPIC 2: BLOOD TRANSFUSION.............................................................................................. 7

TOPIC 3: DISORDERS OF HAEMOSTASIS ...............................................................................10
3.1. Disorders of Coagulation Factors ..........................................................................10
3.2. Disorders Of Platelets .........................................................................................14

TOPIC SUB-HEADINGS INCLUDE:

KEY ISSUES

SELF TEST TASKS

MULTIPLE CHOICE QUESTIONS

CASE SCENARIOS

REFERENCES

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

GOALS AND OBJECTIVES

• This module is designed to be studied in conjunction with your reference texts, including the relevant
chapters in Toouli J et al, Integrated Basic Surgical Sciences, Arnold, London, 2000.

• The module looks at key issues involved in transfusion of blood and blood products, and at disorders of
blood cells and of haemostasis from the viewpoint of the HMO attending patients in hospital practice.

• Self-test tasks are provided for you to check your progress.

• The module’s content relates particularly to the Curriculum Objectives in Surgical Pathology, Physiology
and Pharmacology (Pathology 9: 1.4 through 1.6; Physiology 3: 1.1 through 1.8; and in Surgical
Procedures 1.14 through 1.16).

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

INTRODUCTION

The history of blood transfusion practice has been largely dominated by a balance between safety and the
problems of supply of a scarce resource. In the early years of the twentieth century, the discovery of blood
groups made transfusion safe and predictable. The development of anticoagulants made possible the storage
of blood, and the practice of blood banking emerged. Hence, blood could be made more widely available at an
improved level of safety compared to previous times. Later, blood fractionation techniques allowed the use of
component therapy such as fresh frozen plasma, platelets and gamma globulin for specific indications, further
reaping the benefits of homologous blood.

The increasingly widespread practice of safe elective surgery, as well as wartime demands, have increased the
need for a ready supply of blood. In some areas, the inequities between blood supply and demand initially
resulted in unsound practices with regard to donor selection, blood labelling, and blood dispensing. Although
the problems of disease transmission by blood transfusion were recognised early, in particular with regard to
hepatitis, it was not until the devastating consequences of HIV transmission were realised that the importance
of strict donor selection was enforced.

The requirement of a donor declaration for high risk of viral carrier status, as well as serological testing of all
donations, have significantly minimised the risk of disease transmission. Furthermore, strict control over
storage techniques, clerical checking, and general awareness of all potential complications of blood product
transfusions have increased safety at all levels.

The development of autologous blood transfusion can minimise, but does not completely eliminate, the risk
of viral transmission. Clerical error can still result in transfusion of the wrong blood. Although directed blood
donation is an alternative, directed donations may increase the possibility of the donor making a false
declaration with regard to high-risk behaviour, thus increasing the chances of transfusing contaminated blood.

The safety of our modern blood supply has reached a level not previously seen in the history of medicine.
Nevertheless, the lessons of the past should not have to be learned again. Constant vigilance is required to
recognise and act quickly on the emergence of any new dangers, or the re-emergence of old ones. Prevention
is still the best cure. Every time a transfusion is considered, one must ask the questions ‘is there an
alternative?’ Despite the relatively low risk of transfusion in the modern age, the risk can never be reduced to
zero. For every unnecessary transfusion avoided, the risk to the patient is reduced to zero. There is less
demand on a scarce product, and more resources can be allocated into making the product safer. Every

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opportunity should therefore be taken to reduce the need for blood transfusion. The use of red cell saving
devices, intra-operative haemodilution, haemostatic agents, and the adoption of strict transfusion criteria are all
aimed at reducing the need for blood transfusion to a minimum.

Overall, it must not be forgotten that the transfusion of blood products is frequently a life-saving procedure, even
though blood transfusion will never be completely hazard free. Although media attention tends to highlight
adverse reactions, many patients benefit daily from modern safe transfusion practices. The future challenge is
to ensure that every transfusion is justified, and that where possible every patient is informed of the risks and
alternatives to blood transfusion. For every adverse transfusion-related event, we should ensure that every
possible step was taken to prevent that adverse event, and that the procedure was in fact justified.

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TOPIC 1: DISORDERS OF THE BLOOD CELLS

KEY ISSUE

Pre-operatively the surgeon must assess the patient’s complete blood examination and be alert to
abnormalities; these include anaemia, polycythaemia, neutropenia, neutrophilia,
thrombocytopenia and thrombocytosis.

1.1. Anaemia

A patient with anaemia may require transfusion with red cells pre-operatively. However, if anaemia is not
compromising cardiovascular function, transfusion to a normal haemoglobin pre-operatively is no longer
considered mandatory. Importantly, steps must be taken to ascertain the cause of the anaemia.
Important causes to exclude include blood loss, haemolysis, anaemia of chronic disease, iron deficiency,
B12 or folate deficiency. Similarly, the decision to transfuse postoperatively rather than allowing patients
to make their own red cells should be taken after consideration of the degree of anaemia and the
cardiovascular and respiratory status. A haemoglobin as low as 70 G/L (7gm/dL) can be tolerated if the
cardiovascular respiratory status is normal.

1.2. Polycythaemia

Polycythaemia prior to surgery should be recognised, and treated if appropriate. If the likely diagnosis is
polycythaemia vera, delay of surgery for at least some days until the haematocrit can be lowered by
venesection is important. Polycythaemia due to dehydration can be corrected more rapidly. If secondary
to hypoxia, polycythaemia may be an appropriate adaptation to improve oxygen delivery to the tissues.

1.3. Neutropenia

Causes of severe neutropenia include drug-induced neutropenia, and a variety of bone marrow disorders.
Neutropenia may be one feature of acute leukaemia, due to the disease itself or to treatment with
cytotoxic agents. Surgery will be complicated by the potential for severe infection and absent or delayed
healing. The necessity for surgery should be reviewed and an opinion sought from a haematologist. The
neutropenia may respond to G-CSF (granulocyte colony stimulating factor).

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1.4. Neutrophilia

Neutrophilia may be a response to inflammation due to infection, infarction or malignancy. In occasional

cases it is a presenting feature of chronic myeloid leukaemia.

1.5. Thrombocytopenia

Severe thrombocytopenia may be drug-induced, due to marrow suppression, or to increased destruction

due to a drug-induced immune reaction, particularly after administration of quinine, quinidine or heparin.
Thrombocytopenia may be part of the blood picture of acute leukaemia, or a side effect of cytotoxic drugs.
If the platelet count is less than 50,000 per cubic millilitre (< 50 x 109/L) due to a platelet production
problem, platelet transfusion should be given prior to invasive procedures. Where there is platelet
dysfunction a platelet count of more than 50,000 may not be sufficient, and platelet transfusion may be
required.

Unfortunately in many cases the infusion of platelets does not produce a sufficient increment in the platelet
count because of the presence in the blood stream of antiplatelet antibodies due to previous transfusions
of red cells or platelets. A common error is to administer platelet transfusion in cases where the
thrombocytopenia is due to an antiplatelet antibody, as in idiopathic thrombocytopenic purpura (ITP). The
platelets usually do not survive long enough to be effective, and the recipient will potentially begin to
develop alloantibodies with the potential to further limit the effectiveness of platelet tranfusion. Therefore in
ITP platelet transfusion should generally be limited to cases where there is life-threatening bleeding.

1.6. Thrombocytosis

An increase in platelet count, generally known as thrombocytosis, may be a response to inflammation,

malignancy, iron deficiency, or splenectomy. It may also be due to the myeloproliferative disorder
thrombocythaemia. A high platelet count predisposes to thrombosis, but in thrombocythaemia there may
also be platelet dysfunction that may lead to excessive bleeding.

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TOPIC 2: BLOOD TRANSFUSION

The term blood transfusion is now almost a misnomer. This is because transfusion of whole blood is
increasingly uncommon. Modern transfusion therapy is based on the need for specific components, and
transfusions are given as red cells, platelets or fresh frozen plasma. In cases requiring massive tranfusion, both
red cells and plasma are given. As much plasma as possible is sent for fractionation to produce components
such as albumin, gamma globulin, and factor VIII and factor IX concentrates.

A knowledge of the risks and benefits of transfusion of blood products is important. They are an important
resource and must be used with due consideration for their cost and the fact that they are donated by
volunteers.

It is important to understand the differences in clinical practice involved in the administration of different blood
components and plasma fractions. An important aspect of this is the differing half-lives of the various blood
cellular components (red cells, platelets, leukocytes) and the blood coagulation factors; particularly factor VIII,
fibrinogen and the vitamin K-dependent factors. For instance, because red cells have a life-span of 120 days,
the interval between transfusion of these cells can be relatively long (eg four to six weeks if there is no red cell
production by the bone marrow). Platelets, on the other hand, have a half-life in the blood stream of three to
four days, and if there is no marrow production must be transfused about every two to four days. In addition,
the patient often develops alloantibodies (commonly anti-HLA antibodies) directed against donor platelets
rendering their half-life even shorter. Similarly, for coagulation factors, the frequency of infusions depends on
the half-life. For instance, for factor VIII the half-life is about twelve to sixteen hours, and therefore to cover
surgery in a patient with haemophilia A the coagulation factor VIII may be infused several times daily, and is
often administered as a continuous infusion.

Transfusion of the cellular components and some of the plasma fractions can be complicated by the
development of alloantibodies. Red cells have surface antigens (A, B, Rhesus) that can usually readily be
matched to suitable donors, whereas platelets (and white cells) have the complex and diverse HLA antigen
system. With red cells it is almost always possible to find compatible donors, even when transfusions have
been carried out frequently for many years. However, for platelet transfusions the HLA antigens prevent the
selection of compatible blood donors, with the ultimate development of alloantibodies that limit or prevent an
adequate response to transfusion of these cells. Also, in some patients with haemophilia A or B, antibodies
known as inhibitors develop, and render infusions of factor VIII or IX relatively or completely ineffective.

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Patient consent to blood transfusion is an important issue. Where blood tranfusion may be required during or
after surgery, consent should be obtained before the surgery. This issue should be discussed with the patient
when the surgery is being planned. Where appropriate the possibility of autologous transfusion should be
explored. The signing of the consent form on the night just before the surgery is only the final step in the
process of consent. When blood tranfusion is administered it is most important to document in the case-file
the reason for the transfusion, and to explain the necessity for the transfusion to the patient.

The main cause for patient anxiety related to transfusion of blood products is the possibility of the transmission
of viral infection. In relatively recent times tranfusion-related transmission of hepatitis B, C and of HIV have
occurred. Until testing to identify hepatitis C antibody in the plasma of blood donors was introduced in the early
1990s, there were many cases of transmission of this virus. Although in Australia the risk of transmission of
one of these viruses by blood components is now very small, these potential risks must be explained to the
patient.

Common complications of transfusion of blood component are febrile reactions and urticaria. Fever during
transfusion of red cells or platelets is usually due to the infusion of contaminating white cells, and can usually
be prevented or greatly ameliorated by including a white cell filter in the infusion line. More effective is the
removal of the white cells when the blood is collected from the donor, and this procedure is likely to become
more available and widespread in the near future. Urticarial reactions are usually due to a hypersensitivity
reaction to plasma proteins.

A major complication of red cell transfusion is a haemolytic transfusion reaction. This may present as any
one or all of fever, shock, dyspnoea, severe bleeding, back pain and may lead to jaundice, renal failure or death.
When this medical emergency occurs or is suspected, the transfusion must be ceased immediately. The
identity of the blood and the patient must be checked. The suspect unit must be returned to the transfusion
service for repeat typing and bacteriological culture, and blood and urine from the patient examined for free
haemoglobin.

Two main sources of error that lead to the risk of a haemolytic transfusion reaction are failure to check that:

♦ the blood specimen obtained from the patient for cross-matching is from the correct patient; and
♦ the blood is administered to the correct patient.

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KEY ISSUE

For blood collection there must be a three by three way check. Three pieces of information
(Surname, Christian name, and either UR number or date of birth) must coincide on three objects
(request form, wrist-band, and sample tube). Failure to observe these simple precautions is dangerous
and unnecessarily frequent. Similarly, the information on the blood pack must match the recipient’s
identifying details, and must always be checked against the wrist-band.

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TOPIC 3: DISORDERS OF HAEMOSTASIS

An understanding of disorders of haemostasis is important in surgical practice. Ideally, the disorder should be
detected pre-operatively. However, in some cases the bleeding tendency presents as excessive bleeding
during or after surgery.

3.1. Disorders of Coagulation Factors

Disorders of coagulation factors are either acquired or inherited. In acquired disorders the history of
excess bruising or bleeding is usually short, whereas in hereditary disorders the history is usually life-long.

3.1.1. Acquired Coagulation Disorders

The acquired disorders include:

• Vitamin K deficiency and warfarin overdosage
• Liver disease
• Inhibitors of blood coagulation
• Massive transfusion
• Disseminated intravascular coagulation

A. Vitamin K deficiency and warfarin treatment

Vitamin K deficiency. This is quite common in patients who have not eaten for several days,
and is more likely if starvation or poor intake extends for a week or two. Therefore, it occurs in
patients with nausea, vomiting or anorexia, or patients in an intensive care situation. Bile is
necessary for absorption of vitamin K, and vitamin K deficiency occurs with obstructive
jaundice. Generally, vitamin K may be given orally or parentally; but in obstructive jaundice
must be given parenterally. Vitamin K given intramuscularly is not always effective because it
may be lost in a haematoma formed in the muscle at the site of injection. The intravenous or
oral routes are often preferable. If given intravenously, vitamin K should be mixed thoroughly
with saline (or with water for injection) and administered slowly (not faster than 1mg/min). In
patients who remain very ill for more than a few days, and in patients on parenteral nutrition
therapy, vitamin K should be given prophylactically. Parenteral nutrition fluids should include
water-soluble vitamin K additives.

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Vitamin K is not useful in liver disease as such, unless there is a component of biliary
obstruction.

Warfarin treatment. More commonly the surgeon is confronted with the necessity for surgery
(elective or emergency) in a patient who has been treated with warfarin, or who has warfarin
overdosage. Warfarin is a vitamin K antagonist, and induces a deficiency of factors II, VII, IX
and X, the same factors as are decreased in vitamin K deficiency. As with vitamin K
deficiency, the coagulation defect due to warfarin can be reversed by administration of vitamin
K.

KEY ISSUE

Where urgent surgery is required in patients with vitamin K deficiency or on warfarin

treatment, it may be advantageous to also give prothrombin complex concentrate, which
contains factors II, IX and X. In addition, 2-4 units of fresh frozen plasma may be beneficial.
The effects of these agents, and of vitamin K administration, should be monitored by the
prothrombin time (INR).

B. Liver Disease

All coagulation factors are produced in the liver. In severe liver disease the prothrombin
time is prolonged (PT, INR), and often also the activated partial thromboplastin time (APTT).
In some cases the fibrinogen level is also reduced. Haemostasis may be improved by the
administration of fresh frozen plasma. In liver disease there may be enhanced fibrinolysis
and poor platelet function, further enhancing the defect in haemostasis. Thrombocytopenia is
common. Unfortunately, although coagulation factors II, IX and X are often reduced,
prothrombin complex concentrates are contraindicated because they are thought liable to
precipitate thrombosis or disseminated intravascular coagulation in patients with severe liver
disease.

C. Inhibitors of Coagulation

The commonest inhibitor to coagulation is the lupus anticoagulant. This prolongs the
activated partial thromboplastin time, but predisposes to thrombosis rather than haemorrhage.
Once the diagnosis of lupus anticoagulant is made, it is safe to proceed with surgery,
although the chance of post-operative venous thrombosis may be enhanced.

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Rarely a prolonged APTT is due to an inhibitor to coagulation factors, usually to factor VIII.
This is an autoimmune condition, and may cause very severe bleeding during and after
surgery.

Prolongation of the APTT prior to surgery should be investigated before surgery proceeds.
This requires the involvement by a haematologist expert in coagulation disorders and the
availability of a reference coagulation laboratory. In cases of difficult to diagnose coagulation
inhibitors, it may take a day or more to properly define the problem before surgery can
proceed.

D. Massive Transfusion

KEY ISSUE

Massive transfusion is common, particularly after severe trauma. Massive transfusion is

defined as the transfusion of more than one blood volume in 24 hrs. However, the
patients who pose a major problem are those who lose more than one blood volume (often
several blood volumes) over only a few hours. In these patients the blood loss must be
replaced with both red cells and fresh frozen plasma. At least one unit of fresh
frozen plasma should be used for every two units of red cells. Progress should be
monitored with platelet count, prothrombin time and APTT at approximately every 10 units
of red cells (or one blood volume). After transfusion of one blood volume, administration of
platelet concentrate is advisable, and further transfusions of platelets should be given
depending on platelet counts. If the INR and APTT become significantly prolonged, more
fresh frozen plasma should be given.

E. Disseminated Intravascular Coagulation

In this condition blood coagulation, accompanied by fibrinolysis, occurs in vessels throughout

the body. Thrombi may occur in large or small vessels leading to organ ischaemia. In
addition, coagulation factors and platelets are depleted leading to a bleeding tendency. The
condition is suspected when there is combination of prolonged clotting times,
reduced fibrinogen and thrombocytopenia. Causes include:

• Gram negative or Gram positive septicaemia

• Snake bite
• Pre-eclampsia, abruptio placentae, amniotic fluid embolism
• Heat stroke
• Malignancy

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• Promyelocytic leukaemia

KEY ISSUE

The treatment is to treat the cause where possible. In particular, the patients should be treated
with antibiotics for Gram positive or Gram negative infections. Heparin has been advocated, but
is probably ineffective except possibly in some less fulminant or chronic cases. Coagulation
factors including fibrinogen and blood platelets should be replaced.

3.1.2. Hereditary Coagulation Disorders

The most important of hereditary coagulation disorders are haemophilia A and B, sex-linked
inherited disorders in which there is deficiency of factor VIII or factor IX respectively. Haemophilia
A occurs in approximately 1 in 10,000 in the population, and haemophilia B in about 1 in 30,000.

Patients with severe haemophilia suffer from spontaneous bleeding, particularly into joints and
muscles. The factor VIII is undetectable (<2%). In patients with moderate haemophilia, the
factor VIII level is between 2-5% of normal, and they suffer bleeding after only minor trauma. The
most common form of haemophilia is mild haemophilia where the factor VIII levels are greater
than 5%. These patients suffer haemorrhage after trauma, particularly sporting injuries, dental
extractions, and surgery.

Surgery in these patients should be planned, where possible, well in advance. It is important to
have a detailed protocol devised by a haematologist, and the surgery should be carried out in a
hospital where there is a haemophilia centre and where sophisticated laboratory facilities are
available. For most surgery it is important to raise the level of factor VIII to between 60-100%, and
the treatment must be continued for many days after the surgery (eg 7-10 days), to avoid delayed
haemorrhage. Remember that it requires almost as much factor VIII to raise the level from 0 to
100% (as in severe haemophilia), as to raise it from say 7% to 100% (as in mild haemophilia).
Therefore, for safety in surgery, mild haemophilia is as difficult to treat as severe
haemophilia.

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3.2. Disorders of Platelets

Disorders of platelets are best divided into:

• Thrombocytopenia
• Disordered platelet function

3.2.1. Thrombocytopenia

Probably the most common cause of thrombocytopenia is idiopathic thrombocytopenic purpura

(ITP). This is an autoimmune condition. It may be acute (self-limited) resolving in about one to four
weeks, and this is more common in children. In adults the condition is most often chronic, and
often persists unless treated by splenectomy. Most cases are treated initially with high doses of
prednisolone, and often with intravenous immunoglobulin. If the condition fails to resolve after three
months, and the patient is still requiring high doses of steroids, splenectomy may be indicated.
Splenectomy is effective in about 70% of cases. Patients who do not respond to splenectomy are
difficult to manage, and may require prednisolone and other immunosuppressive agents such as
azathioprine over many years.

Prior to surgery in these patients, it is desirable to gain an elevation of the platelet count, to say
>75,000 per cubic millilitre (>75 x 109 per litre). This is often done by utilising a relatively high dose
of steroids for seven to ten days prior to surgery. In patients resistant to steroids, or in whom
prednisolone has life-threatening side effects (such as patients with diabetes), intravenous
immunoglobulin may be used. It should be realised that intravenous immunoglobulin is
expensive and in limited supply, and is therefore not the first agent of choice.

Other causes of thrombocytopenia include drug-induced thrombocytopenia (eg from quinine,

quinidine, heparin).

In heparin-induced thrombocytopenia syndrome, severe arterial or venous thrombosis is

common. Thrombocytopenia also occurs in liver disease , acute and chronic leukaemias,
myeloproliferative disorders, and myelodysplasia. It may occur during sepsis, or DIC. Some
cases are hereditary, either as autosomal dominant or recessive.

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KEY ISSUE

A mistaken belief is that platelet transfusions are required as automatic treatment for
thrombocytopenia prior to surgery. It is most important to realise that in many patients the platelets
will be destroyed by circulating antibodies. This occurs for instance in ITP, and also in patients who
have received many previous blood transfusions. The latter patients have antibodies against
platelets, usually against the HLA system. It is often very difficult, if not impossible, to find a donor
whose platelets will be suitable. Therefore, one cannot rely on the platelet transfusion to correct the
deficiency in such patients. A haematologist with expertise in this area should be consulted prior to
surgery.

3.2.2. Platelet Dysfunction

Platelet dysfunction is common in patients with leukaemia, myeloproliferative disorders,

myelodysplasia, uraemia, and liver disease . In addition, drugs, particularly non-steroidal drugs
such as aspirin, cause platelet dysfunction. In these patients, the platelet count is not a guide to
the ability of the platelets to effect haemostasis. Even patients with a high platelet count may have
greatly decreased platelet function. Remember that as in thrombocytopenia, the transfusion of
platelets may not be effective.

Platelet function in many conditions (eg uraemia and hereditary platelet dysfunction) may be
improved by infusion of desmopressin. In addition, inhibitors of fibrinolysis such as aminocaproic
acid or tranexamic acid may be helpful.

• von Willebrand disorder

von Willebrand factor is a cytoadhesive which circulates in the plasma as a high molecular
weight polymer, and is also contained in platelet storage granules. It is released from the
platelet storage granules when the platelets undergo the release reaction during platelet
aggregation. von Willebrand factor is important in the adhesion of platelets to surfaces. In
addition, von Willebrand factor carries factor VIII in the bloodstream, and stabilises it.

In von Willebrand disorder there is a decreased level of von Willebrand factor. Because von
Willebrand factor carries factor VIII, the level of the latter substance is also reduced.

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In type I von Willebrand disorder there is a mildly decreased level of von Willebrand factor and
factor VIII. The condition is inherited as an autosomal dominant. Generally speaking, this
disorder leads to only a mild bleeding tendency. Treatment is with desmopressin which raises
the level of factor VIII and von Willebrand factor prior to surgery.

In type II von Willebrand disorder there is decreased function of von Willebrand factor,
whereas the amount of von Willebrand factor may be normal or only slightly decreased. This
condition is inherited as an autosomal dominant.

Type III von Willebrand disorder is inherited as an autosomal recessive, and in this condition
the levels of von Willebrand factor and factor VIII are undetectable. It is much less common
than type I or type II.

KEY ISSUES

Investigation of Patients for a Bleeding Disorder

• A thorough history is the most important and essential initial step. This should include a detailed
history of previous episodes of surgery and dental extraction. For each episode of surgery it
should be recorded whether bleeding or bruising was excessive, whether blood transfusion was
used, whether the patient had to be taken back to theatre, and whether the haemorrhage was
primary (occurring during the surgery), or delayed haemorrhage (occurring hours (reactionary) or
days (secondary) after the surgery). Primary haemorrhage indicates a disorder of platelets or von
Willebrand factor, whereas delayed haemorrhage is more consistent with a disorder of coagulation
factors such as haemophilia. After surgery in haemophilia A & B, delayed haemorrhage may
occur many days after surgery, often after five to ten days. Therefore factor VIII or IX cover may
be required for up to two weeks after surgery.

• A family history of similar events is also very important.

• The patient should have the basic investigations of prothrombin time, APTT and platelet
count. However, these may be normal in many of the hereditary disorders. Where the history is
suggestive it is very important to proceed with special tests including assays of coagulation
factors, platelet aggregation, and von Willebrand factor. These investigations are best
carried out in consultation with a specialist haematologist.

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REFERENCES

Catley L, Lloyd J and Davis K, ‘Blood Transfusion: Blood Products and Alternatives’ in Toouli J et
al, Integrated Basic Surgical Sciences, Arnold, London, 2000; Chapter 28.

Catley L and Lloyd J, ‘Haematology investigations’ in Toouli J et al, Integrated Basic Surgical
Sciences, Arnold, London, 2000.

Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP, Medical Progress: Transfusion Medicine
(First of Two Parts) – Blood Transfusion, New Engl J Med 1999; 340: 438-447.

Metz et al, Appropriateness of transfusion red cells, platelets and fresh frozen plasma, Med J
Aust, 1995; 162: 572-577.

Nelson CL, Bowen WS. Total hip arthroplasty in Jehovah’s Witnesses without blood transfusion,
J Bone Joint Surg (Am), 1986; 68: 350-353.

Whyte G, Savoia H, The risk of transmitting HCV, HBV or HIV by blood transfusion in Victoria,
Med J Aust, 166; 11: 584-586.

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CASE SCENARIO 1
Prior to surgery a patient is found to have platelet count of 20,000 per cubic millimetre.

SELF-TEST TASK 1

1. What factors would you consider important in assessing this problem?

2. What steps could be taken to prepare this patient for surgery?

3. In addition, the patient is found to have an abnormal prothrombin time (INR = 2.6), and an APTT
of 30 secs (normal range 22-36). What are some possible causes of this problem?

4. You suspect vitamin K deficiency, or warfarin overdose. What action would you take?

5. You suspect disseminated intravascular coagulation. What investigative actions would you
take?

6. Liver function tests show that liver disease is the likely cause of the prolonged prothrombin time.
What action would you take prior to surgery?

7. Tests to diagnose DIC show fibrinogen 0.7 g/L, D-dimer >6 microgram/L. Do these results
confirm the presence of DIC?

8. How should the DIC be treated?

CASE SCENARIO 2
Bleeding during surgery: Severe generalised bleeding develops in a 54-year-old man during an
apparently uncomplicated hemicolectomy for carcinoma of the colon.

SELF-TEST TASK 2

1. List four likely causes for this problem.

2. Can you think of other possible causes of this problem?

3. What action can be taken to further define the problem?

4. The relatives indicate that the patient has previously been diagnosed with a hereditary bleeding
disorder, which he did not disclose to the attending clinicians on this occasion. What action
should you take?

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

Commentary for Case Scenario 1

1. Cause of the thrombocytopenia may be decreased production from the bone marrow or increased
destruction. Is it antibody-induced as in ITP, could any of the drugs that the patient is taking be
responsible? Is there any evidence of a primary bone-marrow disorder? Is there any evidence of sepsis?

Likely presence of platelet allo-antibodies or auto-antibodies. A history of previous red cell or platelet
transfusion is important.

2. If the diagnosis could possibly be or is ITP, a trial of steroids and / or immunoglobulin.

Knowledge of the platelet increment after platelet transfusion and of platelet survival would be helpful.

3. Liver disease
Warfarin therapy
Vitamin K deficiency
Disseminated intravascular coagulation

4. Administer vitamin K intravenously or orally, and assess effect on prothrombin time. In vitamin K deficiency
correction will be substantial within six hours. Complete correction of the effect of warfarin occurs within 24
hours. If surgery is urgent, consult a haematologist regarding appropriate blood products (fresh frozen
plasma and/or prothrombin complex concentrate) to reverse the coagulation defect more rapidly.

5. Repeat the INR, APTT, or order fibrinogen and D-Dimer.

6. Infuse fresh frozen plasma, with further monitoring by INR. Aim for an INR less than 1.5, if possible.

7. Yes.

8. Suspect septicaemia. Take appropriate cultures including blood cultures. Take appropriate history and
conduct physical examination to seek source of infection. Treat with intravenous antibiotics. Consult with
a haematologist regarding treatment, particularly administration of appropriate blood products such as
platelets, fibrinogen (as cryoprecipitate) and fresh frozen plasma.

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

Commentary for Case Scenario 2

1. Severe thrombocytopenia
von Willebrand disorder
Platelet dysfunction, hereditary or acquired
Haemophilia A or B

2. Other hereditary or acquired coagulation disorders.

3. It is important to obtain in as much detail as possible the personal and family history of bleeding,
particularly previous episodes of surgery and dental extractions (whether bleeding occurred, if so whether
severe and whether taken back to theatre, and whether blood transfusion was necessary). If this is not
recorded in the case-file it is important to contact relatives for information.

Review medications recorded on admission, particularly aspirin and other non-steroidal drugs. This may
also necessitate further information from relatives.

Send blood for complete blood examination and platelet count, prothrombin time and APTT.

4. The relatives may know the nature of the disorder, but frequently give incorrect information.

In the majority of cases the disorder will have been well documented by a specialist Haematology
Department, and the hospital involved should be contacted.

A specialist haematologist should be involved in further management as soon as possible.

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

MULTIPLE CHOICE QUESTIONS

(TYPE X – MULTIPLE TRUE-FALSE)

Q1 Each of the following statements may be True or False

1 Hepatitis G is an important source of hepatitis infection in blood transfusion practice
2 febrile non-haemolytic reactions to donor white cells occur in 1% of all transfusions
3 autologous blood transfusion eliminates the infective risks of blood transfusion
4 urticaria during blood transfusion is usually a reaction to donor white cells
5 neutrophils have a half-life in the blood of 3-4 days

Q2 In a patient undergoing massive transfusion, severe capillary-type oozing develops

1 blood for haemoglobin, platelet count, INR and APTT should be taken immediately
2 transfusion of platelets and fresh frozen plasma should await the assessment of the laboratory
results
3 fresh frozen plasma is indicated even if INR and APTT are normal
4 if INR and / or APTT are prolonged, estimation of fibrinogen is important
5 fibrinogen deficiency may be corrected by administration of cryoprecipitate
6 capillary oozing, especially if accompanied by a falling blood pressure, may be a sign of a
haemolytic transfusion reaction

Q3 The following are true or false for plasma components

1 the half-life of factor VIII infusion is 12 – 16 hours
2 Prothrombin complex concentrates contain factors II, IX and X, and are useful in vitamin K
deficiency, warfarin overdose and patients with haemophilia B
3 Cryoprecipitate contains factor VIII, IX and von Willebrand factor and fibrinogen
4 the main use of intravenous albumin is for nutritional purposes, rather than as a volume
expander
5 fresh frozen plasma contains normal levels of all coagulation factors

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

Q4 In the pre-operative assessment it is important to do which of the following?

1 Perform a routine INR, APTT and /or platelet count on all patients
2 Obtain a personal and family history of bleeding and bruising, particularly with dental
extractions and operative procedures; if positive perform platelet count, INR and APTT and
complete blood examination
3 Referral to a haematologist for special tests of haemostasis may be indicated even if the INR
and APTT are normal
4 If the patient has been taking aspirin, perform INR, APTT and platelet count
5 If the APTT is 43 seconds (normal range 23-35 seconds) surgery should be postponed until the
cause of the prolonged clotting time is determined

Q5 A patient is bleeding excessively post-operatively. INR, APTT and platelet count are normal
1 two units of fresh frozen plasma should be given
2 despite the normal APTT, the patient may have haemophilia A or von Willebrand disorder
3 chronic renal failure is not likely to be a contributing factor
4 a normal platelet count excludes platelet dysfunction as a possible cause
5 if the cause is due to reduced platelet function, an infusion of desmopressin may be helpful

Q6 Prior to elective surgery a patient with myeloproliferative disorder is found to have a platelet count of
65,000 per cubic millimetre
1 surgery should proceed under cover of platelet concentrates
2 surgery should not proceed because the patient may have antibodies to blood platelets
3 a bleeding time estimation may be helpful to assess the degree of platelet dysfunction
4 platelet increments assessed by platelet count at say 10 minutes and 24 hours after infusion of
blood platelets may be helpful to determine management
5 if platelet increments are known to be satisfactory, platelet concentrates need be given only if
bleeding during surgery is excessive

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

Answers

A1 True 2; False 1, 3, 4 & 5.

A2 True 1, 4, 5 & 6; False 2 & 3.

A3 True 1, 2 & 5; False 3 & 4.

A4 True 2, 3 & 5; False 1 & 4.

A5 True 2 & 5; False 1, 3 & 4.

A6 Answer to come.

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 STEM MODULE: HAEMATOLOGY / BLOOD PRODUCTS / TRANSFUSION

SELF-TEST TASK 3

• Study the appended health alert from a state blood bank (September 1999).
• Write a commentary on the benefits and hazards of directed donation from parents to children,
and indicate briefly what criteria you would recommend in relation to this topic.

 Royal Australasian College of Surgeons – April 2000 Page 24 of 24

HEALTH ALERT FOR MEDICAL PRACTITIONERS (FROM DEPT.
OF HUMAN SERVICES)

RARE TRANSMISSION OF HIV THROUGH BLOOD

TRANSFUSION
A patient who was treated at the Royal Children’s Hospital has been infected with HIV after
receiving a blood transfusion. This tragic event is the expression of the limits of safety using all
approved tests and procedures. There was no fault in any of the procedures carried out by the
Blood Bank or hospital. All appropriate infection control measures were observed. This
reinforces the fact that blood is a human tissue and that 100% safety can never be guaranteed
irrespective of use of the most sophisticated available screens.

The donor, who has donated blood over a long period, was in a ‘window period’ when the blood
was given and tested. Donations given in the ‘window period’ although infectious may not be
detected because the infected person has not had time to develop antibodies to the virus, which
are the basis for the screening test. The length of the ‘window period’ varies within individuals
and also changes according to the sensitivity of the HIV test.

With the highly sensitive tests used by the Blood Bank the ‘window period’ for HIV is
approximately 22 days. Blood Bank statistics indicate the potential risk of a donation being in the
‘widow period’ for HIV is one in 1.2 million. The incidence of HIV infection in repeat donors at
the Victorian Red Cross Blood Bank has been estimated as 1.31 per 100,000 person-years
(Whyte, Savoia. MJA 1997; 166: 584-586).

The Blood Bank introduced routine screening of all blood donations for HIV in May 1985.
Almost 14 million donations have been collect and screened by the Blood Bank in the past 14
years. This is the first such case in Australia since the introduction of testing.

No other patients have been affected, as this patient was the only one who received the
unit of infected blood.

A new test – Nucleic Acid Test (NAT) – which reduces the ‘window period’ for detection of
HIV from 22 to 11 days is in final development stages. This test can detect viruses before
antibodies develop and is proposed to be available for introduction next year.

If patients who have received blood donations present with anxiety relating to this incident, you
can reassure them that the risk from blood tranfusion still remains extremely low.

Information is available by phoning the Blood Bank on (03) 9694 0393. If you require further
information about HIV, contact the Disease Control Section (03) 9637 4181.