BLEEDING

DISORDERS
GROUP 6
GROUP 6 ● ALILAM, Paulyne Joy V.

MEMBERS ●
●
CAPINPIN, Camille Rose O.
CONSTANTINO, Aldrin Rafael S.
● INTERIOR, Nicole Joy A.
BSMT 3 - 1 ● LOMAAD, Jillian B.
SECONDARY
HEMOSTASIS
SECONDARY HEMOSTASIS: OVERVIEW
❏ Secondary hemostasis is the series of interrelated chemical
processes which lead to the formation of durable fibrin strands, as
well as being involved in their incorporation into the existing
platelet plug, creating a fibrin clot.
❏ The fibrin strands themselves are manufactured through the
interaction of various coagulation factors, via a process known as
the coagulation cascade.
❏ Secondary hemostasis is triggered by the release of tissue factor
from epithelial cells that are exposed to the circulation at the
site of vascular injury.
SECONDARY HEMOSTASIS: OVERVIEW
❏ Defects in secondary hemostasis decrease fibrin production and reduce
the stability of the formed clot. In these conditions, bleeding is generally
delayed compared to that observed in defective primary hemostasis. The
loose platelet plug is not stabilized by fibrin strands and starts to leak.
❏ Typical symptoms of patients with defective secondary hemostasis
include:
● Soft-tissue bleeding
● Hematomas
● Retroperitoneal bleeding, or hemarthrosis
SECONDARY HEMOSTASIS
BLEEDING DISORDERS
BLEEDING DISORDER: FACTOR I
AFIBRINOGENEMIA

● Sometimes called congenital afibrinogenemia.

● An inherited blood disorder in which the blood does not clot normally.
● It occurs when there is a lack (deficiency) of a protein called fibrinogen
(or coagulation factor I), which is needed for the blood to clot.
● Afibrinogenemia is thought to be transmitted as an autosomal recessive
trait.
● Treatment may include cryoprecipitate (a blood product containing
concentrated fibrinogen and other clotting factors), fibrinogen
concentrates or plasma (the liquid portion of the blood which contains
clotting factors).
BLEEDING DISORDER: FACTOR I
DYSFIBRINOGENEMIA

● Coagulation (clotting) disorder characterized by having an abnormal form of

fibrinogen.
● Dysfibrinogenemias may be inherited (congenital) or acquired. Congenital
dysfibrinogenemia is rare.
● Congenital dysfibrinogenemias may be caused by mutations in the FGA,
FGB or FGG genes.[1] Inheritance is most often autosomal dominant or
codominant, but can also be autosomal recessive.
● Acquired dysfibrinogenemia is more common than the congenital form
and is associated with liver disease such as cirrhosis, liver tumors, or hepatitis.
● For the remainder, treatment is individualized and depends on the symptoms
and severity in each person.
BLEEDING DISORDER: FACTOR II
PROTHROMBIN (FACTOR II) DEFICIENCY
● A blood disorder that affects the ability of the blood to clot properly. Symptoms of the
deficiency include prolonged bleeding, especially after an injury or after surgery.
● Prothrombin deficiency is caused by changes (mutations) in the F2 gene.
● There are two types of inherited prothrombin deficiency. Type I or
Hypoprothrombinemia and Type II or Dysprothrombinemia. Inheritance of
both types is autosomal recessive.
● A form of the disease that is not inherited (acquired) can be caused by vitamin K
deficiency, liver disease, or an autoimmune response.
● Treatment includes IV therapy using plasma, which is the part of the blood that
contains the blood clotting factors. The blood product that is used is called
fresh frozen plasma.
BLEEDING DISORDER: FACTOR V
FACTOR V DEFICIENCY
● Factor V deficiency is an inherited bleeding disorder that prevents blood clots from
forming properly.
● This disorder is caused by mutations in the F5 gene, which leads to a deficiency of a protein
called coagulation factor V. These mutations prevent the production of a functional factor V
protein, or decrease the amount of the protein in the bloodstream. Mutations are present in
both copies of the F5 gene in each cell, which prevents blood from clotting normally.
● This condition is inherited in an autosomal recessive manner.
● The reduced amount of factor V may lead to nosebleeds, easy bruising, and excessive bleeding
following surgery or trauma.
● Treatment includes fresh blood plasma or fresh frozen plasma infusions during bleeding
episodes.
BLEEDING DISORDER: FACTOR VII
FACTOR VII DEFICIENCY
● Factor VII deficiency is a rare bleeding disorder. May be inherited or acquired.
● The inherited from is caused by mutations in the F7 gene and inheritance is autosomal recessive.
● The acquired form is not inherited and may be caused by liver disease, blood cell disorders,
certain drugs, or vitamin K deficiency.
● The age of onset and severity varies from person to person. While severe cases may become
apparent in infancy, very mild cases may never cause any bleeding problems.
● Signs and symptoms may include nosebleeds; easy bruising; bleeding gums; excessive or
prolonged bleeding after injury or surgery; and heavy or prolonged menstrual bleeding in women.
● Treatment for bleeding may include intravenous infusions of normal plasma, concentrated factor
VII, or genetically-made (recombinant) factor VII. Those with acquired factor VII deficiency due
to vitamin K deficiency may take vitamin K by mouth, injection, or infusion.
BLEEDING DISORDER: FACTOR VIII
HAEMOPHILIA A

● Hemophilia A is an inherited bleeding disorder in which the blood does not clot normally.
● Hemophilia A is caused by having low levels of a protein called factor VIII. Factor VIII is
needed to form blood clots.
● The disorder is inherited in an X-linked recessive manner and is caused by changes
(mutations) in the F8 gene.
● People with hemophilia A will bleed more than normal after an injury, surgery, or dental
procedure.
● This disorder can be severe, moderate, or mild. In severe cases, heavy bleeding occurs after
minor injury or even when there is no injury (spontaneous bleeding). Bleeding into the joints,
muscles, brain, or organs can cause pain and other serious complications.
● The main treatment is replacement therapy, during which clotting factor VIII is dripped or
injected slowly into a vein.
BLEEDING DISORDER: FACTOR VIII
VON WILLEBRAND DEFICIENCY

● Von Willebrand disease is a bleeding disorder that slows the blood clotting process.
● It is divided into three types. Type 1 is the mildest and most common, and type 3 is the
most severe and rarest form. Type 2 (four subtypes) is intermediate in severity.
● This disease is caused by mutations in the VWF gene and can have different
inheritance patterns.
● People with this disease often experience bruising, nosebleeds, and prolonged bleeding
or oozing following an injury, affer surgery, or having a tooth pulled.
● Treatment varies according to the severity of the disease and includes
plasma-derived clotting factor concentrates, and other medications.
● Increased age, pregnancy, exercise, and stress may cause von Willebrand factor levels in
the blood to rise, which can make bleeding symptoms less frequent.
BLEEDING DISORDER: FACTOR IX
HAEMOPHILIA B

● Hemophilia B is a bleeding disorder that slows the blood clotting process.

● Hemophilia B is inherited in an X-linked recessive pattern and is caused by mutations
in the F9 gene.
● People with an unusual form of hemophilia B, known as hemophilia B Leyden,
experience episodes of excessive bleeding in childhood but have few bleeding problems
after puberty.
● People with this disorder experience prolonged bleeding or oozing following an injury or
surgery. In severe cases of hemophilia, heavy bleeding occurs after minor injury or even
in the absence of injury.
● Serious complications can result from bleeding into the joints, muscles, brain, or other
internal organs. Milder forms may not become apparent until abnormal bleeding occurs
following surgery or a serious injury.
BLEEDING DISORDER: FACTOR X
FACTOR X DEFICIENCY

● Factor X deficiency is a rare disorder that affects the blood's ability to clot.
● The inherited form of factor X deficiency (also called congenital factor X deficiency) is caused
by changes (mutations) in the F10 gene and is inherited in an autosomal recessive manner.
● Acquired (non-inherited) factor X deficiency, which is the most common form of the disorder,
generally occurs in people with no family history of the disorder. Acquired factor X deficiency
has a variety of causes including liver disease, vitamin K deficiency, exposure to certain
medications that affect clotting, and certain types of cancer.
● Common features of factor X deficiency may include easy bruising, frequent nosebleeds,
bleeding gums, blood in the urine, and prolonged bleeding after minor injuries.
● Factor X deficiency can be diagnosed based on the symptoms and through laboratory tests to
measure clotting time.
● The goal of treatment is to control bleeding through intravenous (IV) infusions of plasma or
concentrates of clotting factors.
BLEEDING DISORDER: FACTOR XI
HAEMOPHILIA C

● Factor XI deficiency is a bleeding disorder that interferes with the body's clotting
process.
● Although the condition can affect people of all heritages, it is most common in people of
Ashkenazi Jewish descent. Most cases of factor XI deficiency are inherited and caused
by changes (mutations) in the F11 gene.
● In most cases the condition is inherited in an autosomal recessive manner however, it
may follow an autosomal dominant pattern in some families.
● People affected by this condition may have difficulty stopping the flow of blood
following dental extractions, trauma or surgery.
● Treatment is often only recommended during periods of high bleeding risk (i.e. surgery)
and may include fresh frozen plasma and/or antifibrinolytics (medications that improve
blood clotting). Factor XI concentrates may be available for factor replacement in some
countries.
BLEEDING DISORDER: FACTOR XII
FACTOR XII DEFICIENCY
● Factor XII deficiency is an inherited disorder that affects a protein (factor
XII) involved in blood clotting.
● Factor XII deficiency is caused by mutations in the F12 gene. It is inherited
in an autosomal recessive manner.
● While a lack of factor XII does not cause affected individuals to bleed
abnormally, the blood takes longer than normal to clot in a test tube.
● The condition is usually discovered when prolonged clotting is noticed in the
process of running other laboratory tests.
BLEEDING DISORDER: FACTOR XIII
FACTOR XIII DEFICIENCY

● Factor XIII deficiency is an extremely rare inherited blood disorder characterized by

abnormal blood clotting that may result in abnormal bleeding.
● FXIII deficiency is usually caused by mutations in the F13A1 gene, but mutations have also
been found in the F13B gene. It is usually inherited in an autosomal recessive fashion.
● Acquired forms have also been reported in association with liver failure,
inflammatory bowel disease, and myeloid leukemia.
● In affected individuals, the blood fails to clot appropriately, resulting in poor wound healing.
Blood may seep into surrounding soft tissues, resulting in local pain and swelling. Internal
bleeding may occur; about 25 percent of affected individuals experience bleeding in the brain.
● Factor XIII replacement is used to treat bleeding, to prevent bleeding during surgical
procedures, or to prevent recurrent bleeding (such as central nervous system or joint
hemorrhages).
BLEEDING DISORDER: PREKALLIKREIN/
FLETCHER FACTOR
PREKALLIKREIN/FLETCHER-FACTOR DEFICIENCY

● A condition characterized by the congenital or acquired deficiency of prekallikrein. This deficiency is

usually not associated with bleeding.
● The congenital deficiency is very rare. Acquired deficiency may occur in diffuse intravascular
coagulation, infections, and sickle cell disease.
● Prekallikrein deficiency is caused by mutations in the KLKB1 gene, which provides instructions for
making a protein called prekallikrein. The KLKB1 gene mutations that cause prekallikrein
deficiency reduce or eliminate functional plasma kallikrein, which likely impairs the intrinsic
coagulation pathway.
● This condition is inherited in an autosomal recessive pattern, which means both copies of the gene
in each cell have mutations.
● In people with this condition, blood tests show a prolonged activated partial thromboplastin time
(PTT), a result that is typically associated with bleeding problems; however, bleeding problems
generally do not occur in prekallikrein deficiency.
BLEEDING DISORDER: HIGH-MOLECULAR-WEIGHT
KININOGEN (HMWK)/FITZGERALD FACTOR
HMWK/FITZGERALD-FACTOR DEFICIENCY
● A rare autosomal recessive inherited disorder characterized by prolonged partial
thromboplastin time and absence of bleeding diathesis.
● This disease is caused by a defect of Kininogen-1 gene (KGN1).
● A patient with high molecular weight kininogen (HK) deficiency presents with a long
activated partial thromboplastin time (APTT; >60 sec), normal prothrombin time (PT), and
no history of bleeding.
● Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit
abnormal surface-mediated activation of fibrinolysis.
● The existence of HMWK was hypothesised in 1975 when several patients were described with
a deficiency of a class of plasma protein and a prolonged bleeding time and PTT. There is no
increased risk of bleeding or any other symptoms, so the deficiency is a trait, not a disease.
 FACTORS DISORDER

S I Afibrinogenemia
Dysfibrinogenemia

U
II Prothrombin (Factor II) Deficiency

V Factor V Deficiency

M VII

VIII
Factor VII Deficiency

Haemophilia A
von Willebrand Deficiency

M IX Haemophilia A

A
X Factor X Deficiency

XI Haemophilia C

R XII

XIII
Factor XII Deficiency

Factor XIII Deficiency

Y PREKALLIKREIN/FLETCHER

HMWK/FITZGERALD
Prekallikrein/Fletcher Factor Deficiency

HMWK/Fitzgerald Factor Deficiency

VITAMIN K
VITAMIN K: OVERVIEW

● Vitamin K refers to a group of fat-soluble

compounds.
● It is involved in coagulation, bone development,
and cardiovascular health.
● Not typically used as dietary supplement
VITAMIN K: OVERVIEW
● Controls the formation of coagulation factors in
the liver:
■ Factor II (prothrombin)
■ Factor VII
■ Factor IX
■ Factor X
TWO KINDS OF VITAMIN K

● Vitamin K1 (phylloquinone)
● Vitamin K2 (menaquinone)
 VITAMIN K
DEFICIENCY

BLEEDING DISORDER
General Characteristics
● Vitamin K deficiency is rare in adults because many
of the foods we eat contain adequate amounts of K1,
and because the body makes K2 on its own.
● Certain conditions and some drugs can interfere
with vitamin K absorption and creation, making it
possible to become deficient.
General Characteristics
● Vitamin K deficiency is much more common in
infants.
● In infants, the condition is called VKDB, for
vitamin K deficiency bleeding.
● The vitamin K deficiency is rarely encountered
VITAMIN K DEFICIENCY BLEEDING
(VKDM)
● Occurs when babies cannot stop bleeding because
their blood does not have enough Vitamin K to form
a clot.
● The bleeding can occur anywhere on the inside or
outside of the body.
● When the bleeding occurs inside the body, it can be
difficult to notice.
VITAMIN K DEFICIENCY BLEEDING
(VKDM)
● Commonly, a baby with VKDB will bleed into his
or her intestines, or into the brain, which can lead
to brain damage and even death.
● Infants who do not receive the vitamin K shot at
birth can develop VKDB at any time up to 6
months of age.
THREE TYPES OF VKDB
PHYSIOLOGY OF VITAMIN K
DEFICIENCY
Vitamin K1 (phylloquinone)

● Is a dietary vitamin K
● Sources include green leafy vegetables (especially
collards, spinach, and salad greens), soy beans,
and vegetable oils.
PHYSIOLOGY OF VITAMIN K
DEFICIENCY
● Dietary fat enhances its absorption. Infant
formulas contain supplemental vitamin K.
● After the neonatal period, bacteria in the
gastrointestinal tract synthesize vitamin K, which
is absorbed and used by the body.
PHYSIOLOGY OF VITAMIN K
DEFICIENCY
Vitamin K2 (menaquinones)

● Refers to a group of compounds (menaquinones)

synthesized by bacteria in the intestinal tract
● The amount synthesized does not satisfy the
vitamin K requirement.
ETIOLOGY
Neonates are prone to vitamin K deficiency because
of the following:
● The placenta transmits lipids and vitamin K
relatively poorly.
● The neonatal liver is immature with respect to
prothrombin synthesis.
● Breast milk is low in vitamin K, containing about
2.5 mcg/L (cow’s milk contains 5000 mcg/L).
● The neonatal gut is sterile during the first few
days of life.
In adults, vitamin K deficiency can result from
● Fat malabsorption (eg, due to
biliary obstruction, malabsorption disorders,
cystic fibrosis, or resection of the small intestine)
● Use of coumarin anticoagulants
CLINICAL MANIFESTATIONS
The main symptom of vitamin K deficiency is excessive
bleeding. Keep in mind that bleeding may happen in areas
other than at a cut or wound site. The bleeding may also be
apparent if someone:

● bruises easily
● gets small blood clots underneath their nails
CLINICAL MANIFESTATIONS

● bleeds in mucous membranes that line areas inside the

body
● produces stool that looks dark black (almost like tar)
and contains some blood
FOR INFANTS
● bleeding from the area where the umbilical cord is
removed
● bleeding in the skin, nose, the gastrointestinal tract, or
other areas
● bleeding at the penis if the baby has been circumcised
● sudden bleeding in the brain, which is extremely
dangerous and life-threatening
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BSMT 3 - 1
GROUP 6