Bleeding

Disorders
Vascular defects & Coagulation factors
 Under Supervision Of:
Prof. Dr. Mervat Al-Khatib
Internal Medicine Dept.

Presented By:

Muhammad Adel Ali Erfan

Louis Atta-Allah Labib
Muhammad Soliman Haroun
Amr Adel Qandeel
Ahmed Nabil Abu-Emaira

‫محمد عادل على عرفان‬

‫لويس عطاالله لبيب‬
‫محمد سليمان هارون‬
‫عمرو عادل قنديل‬
‫احمد نبيل أبوعميرة‬
Bleeding disorders have been around for thousands of years. According to the National Hemophilia
foundation (NHF), they were mentioned as early as the second century AD in the Talmud, a collection of
Jewish rabbinical writings. When someone has a bleeding disorder, NHF says they usually have a defect in
their blood vessels, or abnormalities in the blood itself.
For most of us, tiny cells in our blood, called platelets, work together around an injury to help form a clot over
the wound. Lack of these platelets or lack of certain clotting factors can cause sufferers to bleed for a longer
period of time.
The cause can be the result of inherited factors, as in case of hemophilia or Von – Willebrand disease, but they
can be non genetic too.

Non – Genetic causes

Hemolytic uraemic syndrome (HUS), is characterized by destruction of red blood cells, damage to lining of
blood vessel walls, low platelet count and in severe cases, kidney failure.
Most cases of HUS occur after an infection in the digestive system caused by Escherichia Coli bacterium
found on contaminated food like meat, dairy products & juice.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) says 90% of children
with HUS who receive careful supportive care survive past the initial stages of the condition, and most of
those will have no long-term effects.

Immune Thrombocytopenic Purpura is another disorder of the blood. Antibodies, part of the immune
system, attach to the blood platelets and cause their destruction.

NIDDK says some cases of ITP are caused by drugs and others are associated with infection, pregnancy or
immune disorders such as systemic lupus erythematosus.

About 50% of cases are classified as “idiopatic”, meaning with unknown reason.

Other non genetic factors listed by NHF, include some of the following reasons for bleeding disorders:
Vitamin K deficiency, liver diseases, various drugs like Aspirin & Warfarin, cancers like Leukemia,
eclampsia as a result of pregnancy or snake venoms.

Genetic causes
The three main types of bleeding disorders with a genetic connection are, hemophilia A, hemophilia B, Von
Willebrand disease.

Hemophilia, according to NHF, is a bleeding disorder caused by a lack of one of the blood clotting factors.
Hemophilia has often been called the “Royal Disease”. It’s genetic in nature, being passed to sons by a
mother who is a carrier of the defective gene. Queen Victoria, who ruled England from 1837 to 1901, passed
the gene on to her daughters who then married into various European royal families.
One of Victoria’s sons had hemophilia & died of a brain hemorrhage at the age of 31. Through a
granddaughter of Victoria, the only son of the last Russian Czar “Nicholas Romanov” was hemophilic.

The National Heart Lung and Blood Institute (NHLBI) estimates that there are about 20,000 hemophiliacs
in the United States. It is thought that about 400 children are born each year with the condition.

Hemophilia A
Hemophilia A is a hereditary disorder with a deficiency in the clotting factor VIII. The end result is excessive
and prolonged bleeding.

NHF says hemophilia A is the most common form of hemophilia, accounting for about 80% of all hemophilia
cases, occurring in 1 out of 10 – thousand live male births and affects mainly men.

Genetics:

Hemophilia A, according to NHF, is caused by a defective gene. Mothers are the carriers of disease. About
half of the male children of female carriers have the disease and half of the female children of female carriers
will be carriers. All female children of fathers with the disease are carriers of the trait, according to NHF.
People with no family history can also develop hemophilia A, NHF says this accounts for a third of all cases.
It usually happens after a new or spontaneous gene mutation.

Symptoms:

The severity of hemophilia A symptoms depends on the type of gene abnormalities and how it affects the
activity of factor VIII. People whose clotting activity is 5% of normal may have mild hemophilia. While they
may rarely have bleeding episodes, NHF says surgery or injury may lead to uncontrolled bleeding which can
be deadly.

NHF says symptoms of hemophilia A include:

(1) Prolonged bleeding from cuts, surgery, and tooth extraction.

(2) Spontaneous bleeding.
(3) Bleeding into joints.
(4) Blood in stool or urine.

NHF says recurring bleeding into joints and muscles can cause crippling deformities. Bleeding can also swell
the base of the tongue and block the airway. Even a slight bump on the head can trigger substantial bleeding
causing brain damage and even death.

Diagnosis:

According to NHF, people with hemophilia A will usually experience their first bleeding episode before they
are 18 months old. A doctor may suspect the disease in a child with unusual bleeding. Often the diagnosis is
made when an infant bleeds excessively following his circumcision. Blood tests can determine whether
clotting is slow. The severity can be determined by measuring the percentage of factor VIII activity in the
blood.

Treatment:

NHLBI says people with hemophilia can lead a somewhat normal lifestyle with a normal life span.
Hemophilia can now be treated by infusing the missing clotting factor. In the 1970’s, factor VIII concentrate
products allowed people with hemophilia A to have home treatment, according to NHLBI. The introduction of
these products also largely put an end to the need for transfusion of whole blood or plasma in the hospital.

NHF recommends hepatitis B vaccine because of the increase risk of exposure to hepatitis from frequent
infusions of blood products. The threat of being infected with HIV has also diminished over the last two
decades according to NHF, by using screening of the donated blood. In the past, NHF says mild hemophilia A
could also be treated with an infusion of cryoprecipitate or desmopressin acetate (DDAVAP). The drugs would
release the factor VIII that the body has stored in the lining of its blood vessels. Today experts may
recommend desmopressin injection or nasal spray.

Hemophilia B
Hemophilia B, according to NHF, is caused by the deficiency of a blood clotting factor known as factor IX.
The disease is also known as Christmas disease; named after Stephen Christmas, a British boy first diagnosed
with the disorder. According to NHF, hemophilia B is:

 a hereditary disease characterized by prolonged bleeding

 affects 1 out of about 35-thousand men
 less common than hemophilia A

Small wounds and injuries are not usually a problem for sufferers of hemophilia B. However, uncontrolled
internal bleeding can lead to permanent damage to joints and muscles, according to NHF.

Genetics:

Just like hemophilia A, hemophilia B is transmitted through the mother who is the carrier of an inherited sex-
linked recessive trait with the defective gene on the X chromosome. Half of the male children of women who
carry the trait will have the disease, and half of the female offspring of female carriers will be carriers,
according to NHF. All female children of a father with hemophilia B will be carriers. Male children of a father
with hemophilia B will be completely unaffected.

Symptoms:

The severity of the symptoms of hemophilia B depends on how the activity of factor IX is affected, according
to NHF. Severe forms of the disease will usually be evident early. Prolonged bleeding typically is noticed
when an infant is circumcised. Mild cases, NHF says, may go unnoticed until later in life, perhaps after a
surgery or trauma. Symptoms according to NHF include:

 Prolonged bleeding.
 Spontaneous bleeding.
 Blood in urine or stool.
 Hemorrhage in gastrointestinal and urinary tracts.
 Nose bleeds
 Bruising.

Diagnosis:

A child whose bleeding is unusual can undergo blood tests to find out if their clotting ability is unusually slow,
according to NHF. If that is the case, a doctor can determine whether the disease is hemophilia B and how the
activity of factor IX is affected.

Treatment:

Infusing the missing clotting factor is the key to treating people with hemophilia B, according to NHF. The
amount depends on a number of factors including:

 Size of the patient.

 Severity of bleeding.
  Location of bleeding.

NHF says the hepatitis B vaccine is recommended for people with hemophilia B because of exposure to blood
products. However, advances over the last 20 years in screening blood donors have increased the safety of
blood products used to treat hemophilia, according to NHLBI.

Plasma and plasma concentrates contain clotting factors and many can be used by patients in their own
homes. To prevent any crisis, NHF says factor IX concentrates can be used at home at the first signs of
bleeding. People with severe forms of the disease may need as many as three infusions a week.

Cautions:

NHF recommends that people with hemophilia avoid situations that might provoke bleeding. They also need
to avoid certain drugs that can aggravate bleeding such as:

 Aspirin.
 Warfarin.
 Heparin.
 Non steroidal anti-inflammatory medications..

Von Willebrand Disease

Named for the Finnish physician who first described the bleeding disorder, Von Willebrand disease is a
hereditary deficiency of the von Willebrand factor in the blood. The factor, according to NHF, is a protein that
affects platelet function. Platelets are tiny particles in the blood that join together at an injury to prepare for a
blood clot, according to NHF. When there is too little von Willebrand factor or the factor is abnormal, the
platelets don't gather properly. The end result is bleeding that doesn't stop as quickly as it should, although it
usually stops at some point. According to NHF, von Willebrand disease:

 is the most common genetic disorder of platelet function

 occurs in 1 to 2 percent of the population
 affects men and women of all racial and ethnic groups

Variations of von Willebrand Disease

According to NHF there are many variations of von Willebrand disease including:

 Type I: Most common and mildest form of the disease. The von Willebrand factor levels are lower
than normal and factor VIII levels may also be low.
 Type II: The von Willebrand factor is abnormal.
 Type III: Severe von Willebrand disease. A total absence of von Willebrand factor and low levels of
factor VIII.
 Pseudo von Willebrand disease: Platelets are defective rather than the von Willebrand factor.
Symptoms:

NHF says von Willebrand disease can be traced through a family's history. Some members of a family will
have symptoms while others may just be carriers of the gene. Symptoms are as follows according to NHF:

 Bruising.
 Recurrent nose bleeds.
 Heavy menstrual periods.
 Longer than usual bleeding after routine surgery.

Diagnosis:

NHF says diagnosing von Willebrand disease can be somewhat challenging. Usually someone who has the
disease has a parent who had bleeding problems. When a physician hears of the symptoms of von Willebrand
disease, like nosebleeds, and easy bruising, NHF recommends that testing be done to determine whether it's
von Willebrand disease. Testing may help discover if the number of platelets is normal but bleeding time is
prolonged.

Treatment:

People with von Willebrand disease have many choices when it comes to treating their disorder, according to
NHF. Some people may never need any treatment. Others can turn to infusions or even a nasal spray to deal
with symptoms and prevention.

The National Hemophilia Foundation's Medical and Scientific Advisory Council (MASAC) recommends
the following:

 A nasal spray or injection of desmopressin acetate (DDAVP).

 Viral-inactivated factor VIII preparations with von Willebrand factor.

NHF says surgery is always a risk for people with the disease, as is menstruation, pregnancy and childbirth for
women diagnosed with von Willebrand disease. Hemorrhage could occur. Using aspirin and any non steroidal
anti-inflammatory can make matters worse, according to NHF

Vascular Defects: (SCURVY)

Scurvy is a condition characterized by general weakness, anaemia, gingivitis and skin hemorrhages caused by
a prolonged deficiency of vitamin C (ascorbic acid) in the diet. Vitamin C plays a crucial role in the formation
of collagen, a major component of connective tissue. Connective tissue has structural & supportive functions
which are indispensable to blood vessels and all tissues within the body. Vitamin C is also important in the
proper functioning of the immune system, iron absorption, cholesterol metabolism and other biological
activities, thus scurvy has widespread effects.

Who gets scurvy? (Susceptible patients)

Scurvy was often seen in sailors on long ocean voyages during the 15th to 18th centuries. Many sailors suffered
from scurvy. The Portuguese navigator Vasco da Gama (1460 – 1524) lost half his crew to the disease during
their voyage around the Cape of Good Hope, and the British admiral Sir Richard Hawkins (1532 – 1595) lost
10,000 sailors to scurvy. In 1747, the British naval physician James Lind conducted experiments to see which
food or liquids might be able to prevent scurvy. He found that lemons, oranges and limes enabled sailors to
recover from scurvy. The nickname of British sailors of “Limey” derives from the practice of giving British
sailors limes.

It’s thought that scurvy occurs very rarely in modern societies of today as most people have access to year
round fresh fruits and vegetables which are rich sources of vitamin C. however; several groups of people are
at risk. These include:

People with chronic malnutrition or those that eat less than 2 servings of fruits/vegetables per day:

 Alcoholics.
 Elderly.
 Men who live alone (bachelor or widower scurvy).
 Children.
 People on peculiar diets or food fads.
 Psychiatric disease (delusions of fear of food, suicide attempt by self starvation, eating disorders).

People with other medical conditions that may prevent the intake and/or absorption of Vitamin C:

 Dialysis patients.
 Inflammatory bowel disease (Crohn’s disease).
 Mal-absorption disorders.
 Severe dyspepsia.

Under developed third world countries where general mal-nutrition exists. Also, in populations that subsist mainly on
cereal grains and without access to fresh fruit or vegetables.

Signs and symptoms of scurvy:

The diagnosis of scurvy is primarily a clinical one, based on a dietary history of inadequate vitamin C intake
and the signs and symptoms described below...

Symptoms of scurvy generally develop after at least 3 months of severe or total vitamin C deficiency. Patients
initially complain of weakness, fatigue, listlessness and aching limbs, especially in the legs. If left untreated,
scurvy can progress to the following more severe problems.
Severe problems of Scurvy:

Skin problems Oral Musculo- Eye Anemia Heart & lung

problems skeletal problems problems
problems
Gums may Bleeding in Patients may This develops in Shortness of
One of the first signs swell and the joints complain of 75% of patients breath, low blood
of scurvy is the become red, causes dryness, as a result of pressure, and
development of soft and spongy. extreme irritation, light blood loss into chest pain leading
perifollicular Any slight discomfort intolerance, tissue, altered to shock and
hyperkeratotic friction may and pain. transient visual absorptions and death.
papules, often on the cause the gums Joints may be blurring and metabolism of
shins. These appear to bleed. Often swollen and stickiness. iron and folate,
as reddish/bluish this results in tender and Haemorrhaging gastrointestinal
bruise-like spots poor oral the pain can (bleeding) bleeding and
surrounding hair hygiene and be so severe beneath the intravascular
follicles. The central dental diseases. that patients conjunctiva and haemolysis.
hairs are twisted like cannot walk. within the optic
corkscrews that may nerve sheath may
break easily. The also occur.
papules may join
together to form large
areas of palpable
purpura or
ecchymoses
(bruises).

Treatment & prevention of Vitamin C

Treatment of scurvy is simply with vitamin C supplements taken orally. The adult dosage is 800-1000 mg/day
for at least one week, then 400 mg/day until complete recovery. Children should be given 150-300 mg/day for
one month. Some improvement of symptoms is usually noticed within 24 hours. Except for the loss of teeth
through dental disease, permanent damage from scurvy does not usually occur.

Prevention of scurvy is easily achieved by take the recommended daily intake (RDI) of vitamin C. This is
between 30-60 mg/day. By following the “5 servings of fruit and vegetables per day” rule, you will be getting
the RDI and maintaining sufficient body stores of vitamin C.
References:
 Book: text book of dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion
RH, Burton JL. Fourth edition. Blackwell Scientific Publications.
 Hirschmann JV, Raugi GJ. Adult scurvy. Journal of the American Academy of
Dermatology 1999;41: 895-906