Download CHAPTER I INTRODUCTION 1.1 Background Hemophilia is a

CHAPTER I
INTRODUCTION
1.1
Background
Hemophilia is a hereditary disease with several manifestation of bleeding due to
impairment of coagulation pathway. The most common symptoms of hemophilia are bleeding in
the joints (hemarthrosis), soft tissue, and muscles that can occur from childhood to adulthood.
Frequent bleeding in the joint that occurred in hemophilia can result in increased susceptibility of
bone fracture.
There are two types of hemophilia; they are hemophilia type A due to lack of F VIII and
hemophilia type B due to lack of F IX. In normal circumstances, when a person experiences a
trauma or injury, the body will trigger the blood clotting system. The ccoagulation cascade will
work to enable all coagulation factors and eventually formed a blood clot of fibrin threads to
cover the wound or stop the bleeding. Conversely in patient with hemophilia, due to the lack of
F VIII or F IX, the formation of blood clots takes longer time and blood clot formation is
impaired. This situation will ineffectively block the blood vessels that are traumatized.
The prevalence of type A hemophilia range from the lowest 1 per 10,000 population to
the highest 1 per 5000 population. It possibly occurs in all ethnic groups. The incidence of
hemophilia B is usually less than one-fifth of hemophilia A. Based on recent data from the
Hemophilia Foundation Indonesia / HMHI Centre of hemophiliacs that have been registered until
July 2005, as many as 895 people suffered from hemophilia spread over 21 provinces from 30
provinces. The national prevalence of hemophilia is only achieve ± 4.1 / 1 million population.1-3
Capital Region of Jakarta is at the highest prevalence of hemophilia (0.29 / 10 000 population).
There are several complications of hemophilia, such as chronic pain due to pressure on
sensory nerves, recurrent bleeding, joint destruction, and also bone fractures. Sometimes surgery
is needed to prevent worsen complications. Surgery in patient with hemophilia requires much
more effort and planning than surgery in non-hemophilic patient. Considering the facts above,
we need to have deeper understanding about the disease of hemophilia. Based on this case, the
author will elaborate more on issues related to surgery in hemophilic patient, as well as some
1
practical issues related to the timing of surgery, preoperative testing, perioperative hemostasis,
and patient rehabilitation.
1.2
1.3
Formulation of the problem

What is hemophilia?

What is the mechanism and management of hemophilia?

What needs to be prepared before and after surgery in patient with hemophilia?
Objective
1.3.1 General Objective

know about the disease hemophilia.

know about the things that need to be prepared for patient who will be doing surgery.
1.3.2 Specific Objective

Knowing the pathophysiology of hemophilia.

Knowing the treatment of patient with hemophilia.

knowing preparation for surgery in patient with hemophilia.
2
CHAPTER II
LITERATURE REVIEW
2.1
Hemophilia
2.1.1 Definition
Hemophilia is a bleeding disease caused coagulation disorder that is lack of bloodderived clotting factors (hereditary) are sex-linked recessive on chromosome X.
2.1.2 Classification
Until now recognized 2 types of hemophilia are inherited sex-linked recessive, namely:

Hemophilia A (classical hemophilia), due to deficiency or dysfunction of coagulation
factor VIII

Hemophilia B (Christmas disease), due to deficiency or dysfunction of F IX (Christmas
factor)
Figure 1. The extrinsic and intrinsic coagulation pathways.4
3
Traditionally, the coagulation cascade was divided into the intrinsic and extrinsic
pathways, based on the relationship of factors to either the PT or PTT (Figure 1). The intrinsic
pathway, which is measured by the PTT, begins with factor XII combining two circulating
factors in the blood and then proceeding through Factors XI and IX until the common pathway
beginning at Factor X is reached. The extrinsic pathway (measured by the PT) begins with factor
VII, which combines with tissue factor in the presence of calcium to activate factor X. Factor X,
the first step in the final common pathway, activates the conversion of prothrombin II to
activated thrombin II with the aid of factor V. Thrombin converts fibrinogen into fibrin leading
to clot formation.5
In reality, coagulation is more a combination of protease, calcium, and cofactor
interactions on the cell membrane and less a series of specific reactions as depicted by the
cascade. It is now thought that the tissue factor (TF) and factor VII pathway is the initiating
event of in vivo blood coagulation. The TF-activated factor VII complex is needed to convert
factor X from an inactive to an active form. Activated factors VIII and IX catalyze this reaction
on cell membranes. Native factor VIII is carried in the circulation in low concentrations bound to
von Willebrand factor. Once activated, factor VIII is unstable and must be bound to factor IX.
Activated factor XIII acts on fibrin to stabilize the clot. In its absence, the fibrin clot is weakened
and wound healing is impaired.5
The cell membrane plays an essential role in the coagulation process. Blood vessel injury
exposes the subendothelium, which contains a variety of substances including collagen, elastin,
and von Willebrand factor. These substances are both potential stimuli of platelet aggregation
and initiators of the coagulation process. Knowledge of these interrelationships can help the
surgeon understand why certain factor deficiencies are clinically important while others are not.
Deficiencies of factors VIII and IX and von Willebrand factor all may produce clinical bleeding
because they are essential components of the coagulation reaction. Deficiencies of factors XI and
XII will prolong the PTT, but do not typically result in clinical bleeding.4 Severity of hemophilia
A and B can be divided into 3 levels, namely: Classification Levels of Factor VII and Factor IX
in the blood.6
4
Patients with severe hemophilia who only had higher levels of factor VIII or factor IX
less than 1% of the normal amount in the blood, can experience internal bleeding a few times a
month. Bleeding can just happen for no apparent reason. Hemophiliac bleeding was less frequent
than severe hemophilia. Bleeding can occur because the body is too heavy activity, such as
excessive exercise. Patients with mild haemophilia bleed less frequently. They experience
bleeding problems only in certain situations, such as surgery, tooth extraction or promising a
serious injury.5
2.1.3 Etiology and Genetics
Females have two X chromosomes, males have one X and one Y chromosome Because
the disease is haemophilia recessive disease (offspring), which can also be caused by a mutation,
a woman carrying defects in one of her X chromosomes (carriers) will not be victims hemophlia
because the other chromosomes will cover up to produce the necessary clotting factors. Another
case when the gene abnormality that is responsible for the production of factor VIII or factor IX,
resulting in males, the X chromosome deficiency is not equivalent to the Y chromosome, so that
lack the gene can not be covered by the dominant allele and the next will be hemofili disease.
Therefor haemophilia is more likely to occur in males than females. Below are two examples of
how the hemophilia gene inherited.5-6
In figure 2, the father does not have hemophilia (ie, he has two normal chromosomes, X
and Y). My mother is a carrier of hemophilia (ie, she has one abnormal X chromosome and one
normal X chromosome). Each girl has a 50 percent chance of abnormal genes inherited from his
mother and being a carrier. Each boy has a 50 percent chance of inheriting the abnormal gene
from his mother and has hemophilia.
5
Figure 2. hereditary disease, linked X chromosome, carrier mother
Figure 3. hereditary disease, linked X chromosome, father with hemphilia
6
Another example (figure 3) that the father has hemophilia (ie, she has one abnormal X
chromosome and one Y chromosome normal). Mother is not a carrier of hemophilia (ie, he has 2
normal X chromosomes). Each girl has a 50 percent chance of abnormal genes inherited from his
father and become a carrier. While each son did not inherit the abnormal gene from his father.
Hemophilia type A is one of a blood clotting disorder caused by deficiency of clotting factor VIII
and the most common form of the disorder, occuring at about 1 in 5000 male births.5-6
2.1.4 Sign and Symtom
Bleeding and bruising are the major signs and symptoms of hemophilia. The most
common signs or symptoms in children and adults are bleeding in the joints (hemarthrosis),
bleeding and bruising in the soft tissue and muscles, bleeding in the mouth from a cut or bite or
loss of a tooth, nosebleeds for no obvious reason, blood in the urine (from bleeding in the
kidneys or bladder) , blood in the stool (from bleeding in the intestines or stomach). Bleeding in
the joints is the most common problem in persons with severe hemophilia. Bleeding often occurs
without an injury. It can go on for days if not treated. Although bleeding can occur in any joint
and the most common places are knees, elbows and ankles.7
2.1.5 Severity of hemophilia
Bleeding in hemophilia can be prevented with clotting factor infusion therapy to achieve
and maintain levels of factor VIII or factor IX (for hemophilia A or B) in normal physiological
levels. But in practice, the achievement of a physiological dose is difficult to achieve. Therefore,
patients with hemophilia have an increased risk for severe bleeding which can be life threatening
in quick time so that it requires emergency treatment. Bleeding in hemophilia patients who could
be among other emergency in the central nervous system bleeding, tracheal bleeding,
gastrointestinal bleeding, organ rupture, compartment syndrome and nerve compression, rupture
pseudotumor, and gravity of ophthalmology (hifema, vitreous hemorrhage, or hemorrhagic
glaucoma).5-7
7
2.1.6 Treatment
To prevent and treat bleeding and bruising in patient with hemophilia type A, factor VIII
is the treatment of choice. One unit of factor VIII is the amount of factor VIII in 1 mL of plasma
(1 U/mL or 1%). The volume of distribution of factor VIII is that of plasma, approximately 50
mL/kg. The difference between the desired factor VIII activity level and the patient's native
factor VIII activity level can be calculated by simple subtraction and expressed as a fraction (eg,
100% - 5% = 95% or 0.95). To find the number of units of factor VIII needed to correct the
factor VIII activity level, use the following formula:
Units factor VIII= (weight in kg) x (50 mL plasma/kg) x (1 U factor VIII/mL plasma) x
(desired factor VIII level minus the native factor VIII level)
The next dose should be administered 12 hours after the initial dose and is one half the
initial calculated dose. Minor hemorrhage requires 1-3 doses of factor VIII. Major hemorrhage
requires many doses and continued factor VIII activity monitoring with the goal of keeping the
trough activity level at least 50%. Continuous infusions of factor VIII may be considered for
major hemorrhage.5-7
2.2
Perioperative Assessment
Pertaining or relating to the period immediately before and/or after an operation, as
perioperative care. Usually relates to immediately before, as in perioperative antibiotics,
extending to just after. 5,8
In order to obtain a successful surgery outcome and maximum result, it takes various
kinds of efforts and plans prior to an operation. one of that, such as preoperative consultation,
where this effort has purpose to:
1. Indentifing diseases and risk factor of the operation
2. To optimize patient condition before surgery.
3. To know and treat condition that can cause post surgery complication
4. To create balance between risk and benefit in the procedure that
5. Act as a team member with anesthesiologist and surgeon.
8
In order to make a good perioperative assessment required anamnesis and physical
examination that is good enough. Anamnesis is to identify any risk factors or kormorbid
conditions that will affecting perioperative risk or that may cause the likelihood of bad outcomes.
Anamnesis is done should be thorough about the heart condition, identify any lung disease,
history of previous thromboembolic events, presence of hypertension, diabetes mellitus and other
atherosclerosis risk factors may indicate the need for evaluation of renal function. To facilitate,
has provided a questionnaire relating to the perioperative (appendix 1).
After anamnesis, then we do a physical examination. In conducting a physical
examination should also be done thoroughly so that no important abnormality is missing. Special
attention is mainly done on vital signs, especially blood pressure. Systolic blood pressure> 180
mmHg or diastolic> 110 mm Hg is generally a contraindication to elective surgery and therefore,
must be treated before surgery is performed. The tests include physical examination of the heart,
lung, liver, and musculoskeletal abnormalities in elderly neuropsychiatric examination
performed for whether there is an acute or chronic cognitive impairment, depression, Parkinson's
disease or focal weakness, which indicates the existence of cerebrovascular disease.
In supporting examination, has the aim to find disease or problem that is not found during
anamnesis and physical examination or to confirm a suspected diagnosis when the history and
physical examination. some supporting examinatio, which is generally done is a complete blood
examination, blood sugar, electrolytes, urea, creatinine, chest radiology and ECG. for another
investigation carried out when there is an indication. 8
2.2.1 Perioperative cardiac evaluation
Perioperative cardiac evaluation must be done carefully depending on the condition of
surgical disease. in cases of acute surgical emergency, praoperatif evaluation limited to a simple
and important tests such as rapid assessment of cardiovascular vital signs, volume status,
hematocrit, electrolytes, kidney function, urine analysis and ECG. just a test and the most basic
intervention that is done until the acute surgical emergency action. Further evaluation can be
done after surgery. in patient with coronary revascularization is not an option, no noninvasive
stress tests are not necessary. the condition is not urgent, praoperatif cardiac evaluation may lead
to consequences such as delaying elective procedures.5,8
9
For perioperative cardiac assessment can be done in several stages (Figure 4). from
alagoritma, we can determine which patient are candidates for cardiac examination.
Figure 4. cardiovascular evaluation algorithm on non-cardiac surgery. 8
The first stage, a consultant is to determine the urgency of non-cardiac surgery. In many
situations, the patient or surgeon-specific factors suggest a strategy that does not wait for further
cardiac assessment or treatment. On the circumstances, the consultant can do best by providing
recommendations for medical treatment of operative.8
The second phase, make sure the patient does not have one of the active cardiac
conditions listed in Table 1. If no then the evaluation can be entered into the third stage. But if
there are any of the conditions mentioned in table 1, resulting in cancellation or postponement of
surgery until the cardiac problem has been clarified and treated adequately. The third phase,
determine the risk factors that will be undertaken. many actions that are associated with
morbidity and mortality <1% (see table 2), even in patient with high risk.
The fourth phase, determine the level of good functional capacity and without symptoms.
functional status can be relied upon to predict long-term cardiac disaster. In asymptomatic
patient with an excellent functional capacity, managing rarely be changed based on the results of
10
further cardiovascular examination. In patient with known cardiovascular disease or at least 1
clinical risk factor, perioperative heart frequency control by sealing the beta quite adequate. 8-9
Table 1. active cardiac conditions in which the patient must undergo an evaluation before non-cardiac surgery. 9
Unstable coronary syndrome

Unstable angina or severe angina pectoralis (ccs class III or IV)

New IMA (>7 days and <30 days) and there were ischemic risks
Congestif cardiac failure, decompensated stadium (class IV NYHA)
Meaningless arithmia:

High degree AV block, Mobitz II of AV block, thirth degree of AV block.

Symtomatic ventricular arithmia that base on cardiac disorder.

Supraventricular arithmia that not controled >100/minutes when rest.

Symtomatic bradicardia

Ventricular takicardia
Severe of valve disease:

Severe aorta stenosis (mean pressure gradient > 40 mmHg, aortic valve or symtomatic

Symtomatic mitral stenosis
The fifth phase, when patient have low functional capacity, symptomatic or functional
capacity is unknown so there are clinical risk factors that will determinepurposes further
evaluation. if the patient has no clinical risk factors, it is sufficient to perform the planned
operation and is not recommended further changes in governance. If the patient has 1 or 2 risk
factors, then can be planned surgery, with cardiac frequency control by sealing the beta or further
investigation if it will change management.
11
Table 2. cardiac risk stratification in non cardiac surgery. 8
Cardiac risks at non-cardiac surgery
High (cadiac risks >5%)

Emergency surgery, major expectially for geriatric

Another major aorta and vascular.

History of old surgery

Loosing a lot of blood and/or electrolite
Moderate (cardiac risks <5%)

Carotid end arterectomy

Head and neck

Intratorak and intra peritoneal

Orthopedi

Prostate
Mild (cardiac risks <1%)

Endoscopy procedure

Supeficial procedure

Katarac

Breasts
2.2.2 Perioperative lungs evaluation
There are three specific factors that are known to increase the risk of postoperative
pulmonary complications, namely: chronic lung disease, obesity and smoking. Patient with
chronic obstructive pulmonary have 2-4 fold risk compared with patient without chronic
obstructive pulmonary.
In patient with asthma have a high risk of bronchospasm during tracheal intubation and
eksturbasi and during the postoperative period. However, in patient with optimal lung function
(based on symptoms, physical examination or spirometry) at the time of surgery, no risk for the
occurrence of other pulmonary complications. Patient with the disease of obesity (weight more
than 113 kg) had 2-fold risk for the occurrence of pneumonia compared with patient whose
weight is lower. Mild obesity is not a significant risk of pulmonary complications. 8,10
12
Based on the research, a smoker is said to increase the risk of postoperative atelectasis. A
smoker is also known to have a 2-fold risk for the occurrence of pneumonia despite treatment of
underlying lung disease. There are two indices that can be used to assist in predicting the risk of
pulmonary complications. The first index that aims to predict the risk of postoperative
pneumonia, and the second index to estimate the risk of postoperative respiratory failure. The
second index is a tool that is helpful to divide the risk of complications pulmonar.
Table 3. pre-surgery risk factors of postoperative pneumonia or respiratory failure after surgery. 8
Preoperative risk factors
Type of surgery
 Aneurisma aorta abdominal
 Toraks
 Upper abdomen
 Neck
 Neurosurgery
 Vascular
Age (years)
 > 80
 70-79
 60-69
 50-59
Functional status
 Totally dependent
 Partially dependent
History of chronic obstructive pulmonary
Blood urea
 < 8 mg/dL
 22-30 mg/dL
 > 30 mg/Dl
Emergency surgery
Loss body weight > 10% in last 6 months
Albumin (<3 mg/dL)
Sensory disorder
History of cerebrovascular accident
Transfution > 4 sack
The use of steroids for chronic disease
General anesthesia
smoking in the past 1 year
alcohol intake> 2 glasses / day in the last 2 weeks
13
Postoperative
pneumonia
Postoperative
respiratory failure
15
14
10
8
8
3
27
21
14
11
3
14
17
13
9
4
6
6
4
-
10
6
5
7
7
6
4
2
3
3
7
4
4
3
3
4
3
2
8
11
9
-
Table 4. risk index to predict post-operative pneumonia or respiratory failure after surgery. 10
Risk of pneumonia
Risk of respiratory failure
0.24 % (0-15)
0.5 % (<10)
1.19 % (16-25)
2.2 % (11-19)
4 % (26-40)
5.0 % (20-27)
9.4 % (41-55)
11.6 % (28-40)
15.8 % (>55)
30.5 % (>40)
Strategies to reduce pulmonary complications such as deep breathing exercises, incentive
spirometry, continuous positive airway pressure, epidural analgesia and selective decompression
nasogastric. 8
2.2.3 Perioperative assessment of the risk of bleeding and thrombosis
Hemostasis consists of 5 components that interact in a balanced and just as important.
component, consisting of primary and secondary hemostasis. primary hemostasis consists of
blood vessels and platelets. secondary hemostasis blood coagulation factors are proteins, anticoagulant and fibrinolysis. interaction of these factors in a balanced form a system that aims to
maintain the blood flow in blood vessels.8
For screening patient with a predisposition to bleeding, especially those without a history
of bleeding is not an easy thing. Therefore it is necessary to anamnesis which was confirmed by
physical examination, and examination of supporting good enough. From history, need to be
asked in the family history of bleeding, history of drug use, especially aspirin and NSAIDs. From
physical examination, is necessary to find the possibility of chronic liver disorders, malignancy,
organomegali, bleeding under the skin to assist in the assessment of the risk of bleeding.
subsequently, the role of routine evaluation of PT, APTT, platelet count, and bleeding time were
also performed to predict the risk of bleeding. But according to research, supporting examination
it is still not entirely satisfactory.
Therefore thrombelastography examination is required, because it can show a better
predictive value. If the value of PT elongated, possibilities that can happen is a disorder that
involves a cascade eksterinsik FII, FV, FVII or fibrinogen deficiency. Possibility of this disorder
14
is APS, vitamin K deficiency, liver dysfunction, fibrinogen deficiency or DIC. If , possibilities
that can happen is abnormalities in interinsik path consisting of FVIII, FX, FXI, FXII or
fibrinogen deficiency. Possibility that occurs in this disorder is caused by the use of heparin,
DIC, hemophilia. 8
Increased risk of perioperative thrombosis is influenced by exposing factors (the factors
that will and are being experienced patient: the type of surgery, infection, immobilization) and
pedisposing factor (factors in patient: Ht, NIDDM, hyperkoagulasi, etc). For the study of risk
factors for venous-thromboembolism (TE) will be able to reduce perioperative morbidity and
mortality, especially patient with moderate to high risk.
In minor surgery with minimal bleeding risk of oral anticoagulants can proceed with
vulnerable INR 1.5-1.8. Operations included here is the excision of skin lesions, biopsy SSTL,
cataract surgery and procedures where bleeding can be overcome by local action.
In major surgery, the strategy does is to prevent thromboembolic events (TE) of more
than bleeding. patient with low risk, do discontinuance of walfarin 5 days before surgery,
without anticoagulation replacement. Patient with high risk should receive a replacement
anticoagulant heparin or LMWH (Table 5).7
Table 5. perioperative anticoagulation recommendations for patient with major surgery.11
Days
-5 (pre op)
-4
Low risk
High risk
Stop walfarin
-
Without anti-coagulan
Stop walfarin
Measuring INR
start a full dose UFH / LMWH which
continued until day -1
-1
Stop LMWH min. 12 hours preop. And UFH
6 hours preop
0
Measuring
INR
in
the
morning and if >2 then delay
Measuring INR in the morning and if >2 then
delay surgery
surgery
+1
Start
walfarin,
when
oral
If hemostasis stable or 6 hours post op. Start
intake allows a dose preop.
LMWH / UFH when INR> 2.0, the delay of
If INR> 1.2 give a smaller
heparin
dose
15
2.3
Perioperative in patient hemophilia
As already mentioned, the bleeding is a major symptom of patient with hemophilia, with
the location of most of the joints (hemartrosis) and muscle. Since bleeding is a major
manifestation of this disease, so careful preparation prior to surgery should be performed on
every patient with hemophilia. Clotting factor should be calculated carefully until 10-14 days
post-surgery because the risk of bleeding that can happen until that period. Therefore,
preparation and good cooperation is a requirement that must be met before surgery is performed
in patient with hemophilia.8, 12-15
In patient who have hemophilia, preoperative preparation requires assessment and good
planning, which includes:
1.
The degrees of haemophilia
2.
Type of surgery: major or minor, elective or emergency
3.
Provision of clotting factor
4.
Complications: inhibitors (anti) factor coagulation existing in these patient, the
approximate length of healing, etc.
5.
Additional therapy
2.3.1 The degrees of haemophilia
People with hemophilia who will undergo surgery, should perform the examination of
factor VIII to determine the degree of haemophilia which aims to reduce the risk of bleeding.
Hemophilia can be divided into 3 categories, the which are:

Mild category, when the levels of factor VIII about 50-40%

Moderate category, when the levels of factor VIII about 1-5%

Severe category, when the levels of factor VIII <1%
Apart from that, need to be asked of factor VIII which has been given and the history of
bleeding to help estimate the weight of hemophilia and bleeding risk that will be faced. 8-6
2.3.2 Type of surgery
Emergency surgery have a risk of complications greater than with elective surgery. In
patient with hemophilia, clotting factor required amount calculated in accordance with the type
16
of surgery (Table 6) or can be calculated using the formula. Keep in mind also the approximate
length of the operation because the operation that lasted a long time sometimes required giving
clotting factor when operation.8
Table 6. the principle of clotting factors in hemophilia patient who will undergo surgery. 16-18
Hemophilia A
Major surgery
Minor surgery
Target F. Coagulation
80-100
40-50
Early doses (F.VIII/KgBB)
40-50
25-40
Maintenance doses (FVIII/KgBB)
20-30
20-30
Duration (hours)
8-12
8-12
2.3.3 Provision of clotting factor
Calculation of the required factor VIII needed a good assessment. If surgery is elective
and is considered relatively high risk of bleeding, surgery should be delayed until the required
number of factor VIII is fulfilled or the patient needs to be sent to another hospital that has more
inventory.8
The formula used to calculate the factor VIII
Factor VIII required = (F. VIII target - current levels of F. VIII) x body weight with a target
of 100% major operations and 50% post-surgery
Very important to prepare the F. VIII until 10-14 days postoperatively. In some cases,
especially in minor surgery with not a lot of bleeding, transfusion F. VIII after the operation
primer wound healed the crioresipitat can be given, depending on the condition of the patient and
the treating doctor's assessment team.8,14
Factor VIII is given immediately before surgery and continued every 8-12 hours
depending on the type of surgery, and postoperative bleeding condition happens. FVIII count this
individual case basis because it depends of weight hamofilia, type of surgery, bleeding and other
conditions in each hospital with emphasis on patient safety.
17
2.3.4 Complications
In patient with severe hemophilia who receive frequent transfusions F. VIII or a history
of repeated bleeding, should be considered the F. VIII inhibitor. If facilities allow, this inhibitor
levels should be checked because it is usually required larger doses in patient who have
inhibitors. Needs to consider also the possibility of other postoperative complications such as
that caused clotting factor half-life becomes shorter and the risk of major bleeding.
2.3.5 Additional therapy
Things that need to be considered as an additional therapy or other action prior to or post
surgery, such as:

Provision of anti-fibrinolytic traneksamat acid 4x500 mg or 3x 1000mg before surgery
until 7-10 days postoperatively

Physiotherapy which require adjustment of the timing of F. VIII krioresipitat
cold compresses and others.
Perioperative planning also must not forget the general principle of handling people with
hemophilia, such as:

Avoid drug acetyl salicylate, anti-platelet aggregation and anticoagulan

Avoid intramuscular injection of drugs

Overcome the bleeding as soon as possible and give a clotting factor in the proper way
Another following issues are of prime importance when performing elective surgery on
persons with hemophilia:

Surgical procedures should be performed in co-ordination with a team experienced in the
management of hemophilia.

Procedures should take place in a centre with adequate laboratory support for reliable
monitoring of clotting factor level.

Pre-operative assessment should include inhibitor screening.

Surgery should be scheduled early in the week and early in the day for optimal laboratory
and blood bank support, if needed.
18

Availability of sufficient quantities of clotting factor concentrates should be ensured
before undertaking major surgery for hemophilia.

The dosage and duration of clotting factor concentrate coverage depends on the type of
surgery performed (see Table 6)
About 10%-15% of hemophilia A patients may develop persistent inhibitors rendering treatments
with factor concentrates difficult. The following should be kept in mind:

The majority of patients who develop inhibitors do so early – within the first 10-20
exposure days.

Patients more likely to develop inhibitors are those with severe gene defects such as gene
deletion or inversion, nonsense, and frameshift mutations.

Inhibitors may be transient despite continual specific factor replacement, usually when
the titre is low (< 5 BU).

Patients whose inhibitor titres are x 5 BU (high responders) tend to have persistent
inhibitors. If not treated for a long period, titre levels may fall but there will be a
recurrent anamnestic response in 3-5 days when challenged again.

For children, inhibitors should be screened once every 3-12 months or every 10-20
exposure days, whichever occurs first, and for adults as clinically indicated.

Inhibitors should also be screened prior to surgery, and when clinical response to
adequate treatment is sub-optimal.

Very low titre inhibitors may not be detected by the Bethesda inhibitor assay, but by a
poor recovery and/or shortened half-life (T-1/2) following clotting factor infusions.
These general principles must be understood by any treating physician, including doctors
who perform anesthesia. While giving blood transfusions or other drugs, according to clinical
indications in patient.
19
CHAPTER III
CASE ILLUSTRATION
Mr. I, 39 years old, live on cempaka putih come with chief complaint would hematoma
on his left thigt that intermitttent since 4 year before hospital admission. From history of present
illness, when patient was 5 years, patient have been diagnosed with disease of hemophilia type
A. since that time, the patient always control to hospital for his disease. patient said rarely suffer
bruise. If there any bruise or hematom, patient given transfusions cryoresipitake and after that
complaints disappeared.
Patient at age 35 years come with hematoma bump on his left thigh. According to the
doctor, the patient's femur easy to fracture and recommended for installation of an implant
operation but the patient refused and asked for transfusion cryoresipitake. These events continue
to repeat for about 4 years until the last patien get hematom bump again with femoral fracture.
until finally the patient's femur have to immediately amputation surgery on his left thigh because
the wound continue worsening. There is no complaint of difficulty in breathing, decrease of body
authoright, chest pain, headache, muscle pain, nausea, or vomiting. There was decrease of
appetite and increasingly authorak.
From history of past illness, patient doesn’t have any history of hypertension, no history
of diabetes mellitus, no history of asthma, no history of allergy/drug allergy, no history of
previous illness of heart or lung and no history of having jaundice. From history of family
illness, in patient’s family doesn’t have any history of hypertension, no history of diabetes
mellitus, no history of asthma, no history of allergy/drug allergy, no history of previous illness of
heart or lung, no history of having jaundice disease. There is history of hemophilia on his
grandfather. Status of patient maried and having one daughter, occupation employees, there no
history of smoke, drinking alcohol, IV drug user or multiple sexual partners, financing with
“Jamkesmas”.
From physical examination, patient looks moderately ill, compos mentis, looks having
adequate nutrition. Blood pressure: 130/90 mmHg, heart Rate: 84x/minute, regular. Respiratory
rate: 20x/minute, temperature: 36.7oC, height: 160 cm, authoright 60 kg, BMI = 23 kg/m2.
20
Author found pales on his skin, extemity and eye’s konjungtiva. From his extremity author found
fracture and hemarthrosis hip joint femur dextra.
From supporting examination, author found that laboratory examination (19/12/2010)
Hemoglobin 10.7 g/dl, hematocrit 34.4%, leukocytes 4200/ul, thrombocytes 279.000/uL,
eritrocyte 4.13, MCV: 53 fL, MCH: 25 pg, MCHC: 32.7 g/dl, Differential count
0.2/1.4/71.9/17.3/9.3, LED: 51 mm, PT: 15.1(11.8), APTT: 58.9(34.4), BT: 3”, CT: 13”,
fibrinogen: 327 mg/dl, D-dimer: 200, Ureum: 35 mg/dl, Creatinin: 0.1 mg/dl, albumin: 4.03 g/dl,
SGOT: 23 u/L, SGPT: 21 u/L, blood glucose: 31 mg/dl. Natrium 132 mmeq/L, kalium 3.67
mmeq/L, cloride 94.8 mmeq/L. Arterial blood gas analysis pH 7.39, pCO2: 41.6, pO2: 102.4,
HCO3: 25.1, SaO2: 97.6. From ECG and thorax photo (19/12/2010) are in the normal range,
The diagnose of the patient from anamnesis, physical examination and supporting
examination. Fracture and hemarthrosis hip joint femur dextra, moderate hemophilia A and
Anemia nomosiklic hipocrom. Treatment for his fracture and hemarthrosis hip joint femur dextra
is by amputation surgery with tolerance of surgery from internist subdivision metabolic is
moderate, from subdivision cardiology is moderate, from subdivision pulmonology it is said that
there are 1.19 % risk for pneumonia and 11.6 % risk for apnea. From subdivision hematology,
moderate to severe risk of bleeding and moderate risk of trombosis. Planned preparation
amputation surgery in this patient :

Day -1
: kegonate 3000 units continue with 1500 units/12 hours

Days 1-3
: kegonate 1500 units / 12 hours

Days 4-6
: kegonate 2000 units/24 hours

Days 7-14
: kegonate 1000 untis / 12h
Observation signs of bleeding, pereated complete peripheral blood examination and
homeostasis after surgery. In addition, patient diagnosed with anemia normositik hipokromik.
given maltofer 3x1 and prepared to pack red cell transfusion.
21
CHAPTER IV
DISCUSSION
This patient came with the chief complaint of having bruise on his left thigh. Actually
this complaint had been occurred several times since 4 year before hospital admission. The
possible differential diagnoses of bruise appearance on skin of this patient are trauma and blood
clotting disorders. Blood clotting disorder can be divided into 2 categories, they are abnormality
of extrinsic pathway (FII, FV, FVII or fibrinogen deficiency) which can be caused by APS,
vitamin K deficiency, liver dysfunction, fibrinogen deficiencyy; and abnormalities in intrinsic
pathway (FVIII, FX, FXI, FXII or fibrinogen deficiency) which can be caused by the use of
heparin, DIC, hemophilia. From anamnesis, this patient said that he has been diagnosed with
type A hemophilia when he was 5 years old. Since that time, he regularly visits the doctor to
control his disease. History of having bruised on the skin since childhood is one of the typical
signs and symptoms of hemophilia. The diagnosis of hemophilia is also supported by the history
of the cryoprecipitate transfusios, which is really help to subside the bruised or hematom of the
patient. From those information we can conclude that the patient is suffering from hemophilia. In
this patient bruises are occurred due to the failure of blood clotting secondary to the deficiency of
blood clotting factors such as FVIII or FIX. This problem usually can be solved by the
transfusion of cryoprecipitate which is enriched for FVIII and FIX. There was also the history of
fatigue and decrease of appetite. They usually found as the symptoms of anemia. Anemia in this
patient is the end result of the frequent blood loss and also could be affected by the decrease of
food intake.
From physical examination, patient looks moderately ill, compos mentis, looks having
adequate nutrition due to the BMI of 23 kg/m2 (height: 160 cm, weight 60 kg). The blood
pressure is 130/90 mmHg with the heart rate of 84x/minute and regular. Respiratory rate is
20x/minute while the temperature is 36.7oC. So, we can conclude that the general conditions and
vital signs are within normal limit, except for the pre-hypertension condition. The prominent
findings in this patient are pale skin, limbs, and conjunctiva. These abnormalities indicate the
low level of hemoglobin in the patient’s blood. Anemia in this patient is caused by frequent
episodes of bleeding due to the hemophilia and could be affected by decrease of food intake. The
22
other hallmark signs of hemophilia found in this patient are the hemarthrosis in the hip joint and
fracture of femur dextra. The repeated or continuous hemarthrosis episodes could eventually
lead to the vulnerability of the bones in the joint and results in fractures. Unfortunately these
terrible complications had been occurred to this patient, and finally the worsening wound in his
thigh cause the tissue necrosis with the high possibility of infection. So, amputation is the best
management chosen to prevent the further ascending infection in this patient.
From supporting examination, hemoglobin result in this patient is 10.7 g/dl, with MCV:
53 fL, MCH: 25 pg, MCHC: 32.7 g/dl. These data give the information for normocytic
hypochromic anemia. If there is no other red blood cells disorder other than hemophilia, the
management plan for this patient is only observation. It means that the signs of bleeding, such as
hematomas, gum bleeding, epistaxis, or hemarthrosis should be monitored adequately. If there
are the evidence of bleeding, the complete peripheral blood examination should be conducted
and if needed the pack red cell transfusion also should be prepared. Ureum, creatinin, albumin,
ALT, AST, electrolytes, and arterial blood gas analysis, ECG and thorax photo are in the normal
range so from that information. The blood glucose level at that time is 31 mg/dL. So the
additional problem in this problem is hypoglycemia that required the infusion of glucose. In this
patient, 40% dextrose bolus infusion followed by dextrose 10% / 12 hours are given before the
surgery conducted. The other abnormality is the prolonged of aPTT: 58.9(34.4). The prolonged
aPTT value inform us that there is the defect in the intrinsic pathway of coagulation pathway. In
hemophilia, there is the deficiency of either factor VIII or IX. In type A hemophilia, like in this
patient, the factor VIII is deficient. This laboratory findings is also supporting the diagnosis if
hemophilia.
Patient with hemophilia is at risk for having fractures around joints or just loss of motion
due to the osteoporotic bone. The actual management of the fracture should be performed in a
appropriate manner. The most important thing is operative treatment under appropriate coverage
of clotting factor concentrates. Fractures in hemophilia patients require immediate factor
concentrate replacement. At least first 50% should be obtained initially and maintained for 3–5
days. Lower levels may be given for 10–14 days for maintenance while the fracture becomes
stabilized. Care should be taken to avoid prolonged immobilization that could lead to significant
23
limitation of range of movement in the adjacent joints and physiotherapy should be started as
soon as the fracture is stabilized.
Preoperative planning is absolutely needed in this patient. In the hospital-based services,
we can arrange the team approach to this patient by request the operation tolerance from
anesthesiology, metabolic, cardiology, pulmonology, and hematology divisions. There are
several indicators determined for the operation risk in this hemophilia patient. The surgery
tolerance from cardiology division is moderate due to low risk factors (below 5%) got by this
patient (table 2). From pulmonology, the risk is 1.19 % for pneumonia and 11.6 % risk for apnea
(table 4). From hematology, this patient have moderate to severe risk of bleeding and moderate
risk of trombosis (table 5). After determination of surgery risk and tolerance, coagulation factors
concentrates should be also prepared adequately. To calculate the required factor VIII needed,
we can use the formula in table 6. The result of calculation in this patient is 3000 units and
continue with 1500 unit/12 hours on day -1. On days 1-3 after surgery, the patient will given
1500 units /12 hours. On days 4-6, the patient will given 2000 units/24 hours, and on days 7-14,
the patient will given 1000 units/12 hours. We also have to observe the signs of bleeding. If there
were any bleeding, we should immediately order the complete peripheral blood examination,
give kegonate transfution, prepare pack red cells, and if necessary consultation with the internist.
24
CHAPTER V
CONCLUSION
Mr. I, 39 years old, came with chief complaint of frequently intermittent hematoma on
his left thigh that had been occurred for 4 years before hospital admission. The diagnosis of the
hemophilia is established based on namnesis, physical examination, and supporting examination.
Frequent hematoma episodes, hip joint fracture and hemarthrosis, normocytic hypocrome
anemia, prolonged aPTT are the findings that support the diagnosis of Hemophilia in this patient.
The preoperative management for this patient is already conducted properly. The chosen
treatment for his hip joint fracture and hemarthrosis is amputation surgery with planned surgery
preparation, such as preparation of coagulation factors, emergency packed red cell, and surgery
risks identification.
Thus, management of pre-operation in patient with hemophilia should be done carefully
and thorough. It all started from systematic history and physical examination to investigate signs
and symptoms of bleeding, prioritizing the laboratory examination, and arrange rational and
well-prepared treatment to prevent the bleeding.
25
REFERENCE
1. Hoots WK. Emergency Care Issues in Hemophilia. In: Treatment of Hemophilia. Canada:
World Federation of Hemophilia; 2007.
2. Oxford Centre of Evidence-based Medicine. Oxford Centre for Evidence-based Medicine
Levels of Evidence (March 2009). Download on December 2010: http://www.cebm.net/
index.aspx?o=1025.
3. Unnamed. Epidemiologi Hemofili di indonesia. 2009.
Download on january 2011:
http://www.umm.edu/altmed/articles/hemophilia-000076.htm
4. Michael Meyer, PhD, Albany Molecular Research, Inc.Technical Report: Volume 7, No.
64, 2002. Page: 379.
5. Bruce D. Speiess, Ricahard K. Spence. Perioperative Transfution Medition 2nd ed.
Lippincott Williams & Wilkins. New york; 2006. Page: 21-44, 379- 386.
6. Behrman RE, Kliegman RM, Jenson HB. Nelson Texbook of Pediatrics. 17th ed.
Philadelphia: Saunders; 2004. Page: 310-11, 1657-1660.
7. Hoots WK. Emergency Care Issues in Hemophilia. In: Treatment of Hemophilia. Canada:
World Federation of Hemophilia; 2007. Page: 130-35.
8. Mandoer, Arif et al. Kedokteran Perioperatif Evaluasi dan Tata Laksana di Bidang Ilmu
Penyakit Dalam. InternaPublishing: 2007. Page 11-49, 202-206
9. Unnamed. CCS: canadian cardiovaskular society; New York Heart Association
10. Azorullah AM, khuri SF, Henderson WG, et al: Ann Intern Med. 2001; 135:847-57
11. Sridhar R, Grigg AP. perioperative surgery Aust Prescr 2000; 23: 13-6
12. Townsend CM. Sabiston Textbook of Surgery 16th ed. Philadelphia: W.B Saunders
Company.2001.
13. Schwartz SI, Spencer S, Galloway DF. Principles of Surgery 7th ed. USA: Mc Graw-Hill;
1999.
14. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in
critically ill patients: a systematic review of randomised trials. Brit Med J. 1998;27:20010
26
15. Dahlan HM, Jusi HD. “Vaskuler”. Dalam: Kumpulan Kuliah Ilmu Bedah. Reksoprodjo S
(Editor). Jakarta: Bagian Ilmu Bedah FKUI/RSCM;1995. Page: 50-57, 241-252.
16. Nillson IM. Bleeding symtom in haemophilia. In: Nillson IM, edtor. Haemophilia.
Stockhom; pharmacia, plasma product 1964; 5: 26-9
17. Berettler DB, Levine PH. Clinical manifestation and theraphy of inherited coagulation
factor deficiency. In: Coleman RW, hirsh J, marder VJ, salzman EW, editor. Hemostatis
and trombosis. Basic principal and clinical practice 3th edition. Philadelphia., JB
Lipinncot company.1994: 8: 169-83.
18. Hillman RS, ault KA, rinder HM. Haemophilia and other intrinsic pathway defect.
Haematology in clinical practice 4th edition. New York., McGraw-Hill 2005.,32:368-79.
27
APPENDIX
Preoperative questionnaires filter
1. Do you ever had a heart attack?
2. Do you ever experience heart problems?
3. Do you ever have heart failure?
4. Do you ever have any fluid in the lungs?
5. Do you have a noise coming from the heart?
6. Do you have had rheumatic fever as a child?
7. Do you ever experience chest pain or a feeling of chest bound?
8. Do you ever treated because irregular heart rhythm?
9. Whether you have high blood pressure?
10. Do you ever have trouble breathing?
11. Do you suffer from asthma, bronchitis or emphysema?
12. Do you often cough?
13. Do you feel difficulty breathing when climbing stairs?
14. Do you feel difficulty in breathing while walking a single block building?
15. Do you currently or have recently smoked a cigarette? if yes, how many packs a day?
how many years?
16. Do you have liver disease or hepatitis or joundis history?
17. Do you drink alcoholic beverages?
18. Do you have indigestion, burning sensation in the chest or the entry of the stomach into
the chest cavity?
19. Do you have a history of thyroid disease or goiter?
20. Whether you have diabetes?
21. Do you have kidney problems?
22. Do you experience numbness or weakness in hands or feet?
23. Do you have epilepsy, fainting or seizures?
24. Do you have problems with blood clotting or bleeding?
28
25. Do you have a medical problem important?
26. If ever undergo anesthesia?
27. Whether there are members who experience side effects during anesthesia?
28. Do you have arthritis or pain in the neck and jaw?
29. Whether you have dentures, patched or removed?
30. Do you think you're pregnant?
31. Do you are undergoing treatment with prednisone or other corticosteroids?
32. Please write a list of foods or drugs that cause your allergies!
33. Please write a list of medications you are taking at this time!
34. Please write a list of operations that you have ever lived before!
35. Do you are operating today, when you last eat or drink!
36. Age:
Weight:
Height:
In patients who answered yes on question # 1-8, 10.14, 16, 19-25 or 30vharus conducted
anamnesis and complete physical examination as part of preoperative evaluation
From Mandoer, Arif et al. Kedokteran Perioperatif Evaluasi dan Tata Laksana di Bidang Ilmu Penyakit
Dalam. InternaPublishing: 2007. Page 11
29