Hemophilia (Year of the Zebra)
Summary
TLDRHemophilia is a genetic bleeding disorder affecting the blood's ability to clot due to deficiencies in clotting factors. The coagulation cascade, involving both intrinsic and extrinsic pathways, is impaired, leading to prolonged bleeding. Hemophilia A and B are caused by mutations in the genes for factors VIII and IX, respectively. Treatment involves clotting factor replacement, but complications like inhibitors can arise. Diagnosis is through lab tests, and individuals with hemophilia should avoid activities that increase bleeding risk.
Takeaways
- 🩸 Hemophilia is a genetic disorder characterized by impaired blood clotting, often due to a deficiency in clotting factors.
- 🛑 Hemostasis is the process that stops bleeding, and in hemophilia, this process is compromised, leading to prolonged bleeding.
- 🧬 The coagulation cascade involves a series of clotting factors that, when activated, form a clot to stop bleeding.
- 🔪 Primary hemostasis involves platelet plug formation at the site of injury, which is often normal in hemophiliacs.
- 🧬 Secondary hemostasis involves the coagulation cascade and is where deficiencies in clotting factors lead to hemophilia.
- 🌐 Hemophilia can be caused by deficiencies in various clotting factors, but most commonly factors VIII (Hemophilia A) and IX (Hemophilia B).
- 🧬 Hemophilia A and B are X-linked recessive disorders, predominantly affecting males due to their single X chromosome.
- 🏥 Diagnosis of hemophilia involves lab tests such as platelet count, Prothrombin time, and partial thromboplastin time, which are often abnormal in hemophiliacs.
- 💉 Treatment typically involves injections of the deficient clotting factor, but can be complicated by the development of inhibitors.
- 🚫 Individuals with hemophilia are advised to avoid activities and medications that increase the risk of bleeding.
- 🧬 Other causes of hemophilia-like symptoms include liver failure, vitamin K deficiency, autoimmunity against clotting factors, and disseminated intravascular coagulation.
Q & A
What is the meaning behind the term 'hemophilia'?
-The term 'hemophilia' is derived from Greek words for 'blood' and 'love,' which metaphorically suggests that people with the condition have a hard time stopping bleeding.
What is the normal process called when the body stops bleeding after an injury?
-The normal process is called 'hemostasis,' which involves immediate vasoconstriction, platelet plug formation known as primary hemostasis, and the activation of the coagulation cascade leading to secondary hemostasis and clot formation.
What are the clotting factors and where are they usually synthesized?
-Clotting factors are a set of proteins in the blood, most of which are synthesized by the liver and are usually inactive until activated during the coagulation process.
How does the coagulation cascade work in terms of amplification?
-The coagulation cascade works through a series of proteolytic cleavages that activate clotting factors in sequence, which has a huge degree of amplification and forms a clot within minutes of injury.
What is the final step in the coagulation process that leads to clot formation?
-The final step is the activation of the protein fibrinogen to fibrin, which polymerizes to form a mesh that reinforces the platelet plug and results in a hard clot at the injury site.
What is the difference between primary and secondary hemostasis?
-Primary hemostasis involves the formation of a platelet plug, while secondary hemostasis involves the coagulation cascade and the formation of a stable fibrin clot.
How does hemophilia affect the coagulation cascade?
-In hemophilia, there is a decrease in the amount or function of one or more clotting factors, which makes secondary hemostasis less effective and allows more bleeding to occur.
What are the two pathways that can initiate the coagulation cascade?
-The two pathways are the extrinsic pathway, which starts with tissue factor exposure, and the intrinsic pathway, which starts with platelet activation near blood vessel injury.
What are the most common types of hemophilia and the clotting factors they affect?
-The most common types are Hemophilia A, which affects factor 8, and Hemophilia B, which affects factor 9.
How are Hemophilia A and B inherited and what chromosomes are the responsible genes located on?
-Both Hemophilia A and B are X-linked recessive conditions, meaning they are inherited on the X chromosome and usually affect men, who have only one X chromosome.
What are some of the complications that can arise from hemophilia?
-Complications of hemophilia can include easy bruising, hematomas, prolonged bleeding after injuries or surgeries, gastrointestinal bleeding, severe nosebleeds, and dangerous bleeding into joints or the brain.
What are the typical diagnostic tests for Hemophilia A and B?
-Diagnosis usually starts with lab tests including a platelet count, Prothrombin time (PT), and partial thromboplastin time (PTT), followed by specific factor activity tests and mutation testing of the clotting factor genes.
How is hemophilia typically treated and what challenges can arise with treatment?
-Hemophilia is typically treated with injections of the missing or non-functional clotting factor. Challenges can include the development of inhibitors by the immune system, which can diminish treatment effectiveness and sometimes cause severe allergic reactions.
What is the role of desmopressin (DDAVP) in treating mild Hemophilia A?
-Desmopressin (DDAVP) is helpful for patients with mild Hemophilia A as it stimulates the release of Von Willebrand factor from endothelial cells, which promotes the stabilization of residual Factor 8.
What lifestyle recommendations are there for individuals with hemophilia?
-Individuals with hemophilia should avoid contact sports and medications that promote bleeding, such as aspirin.
Outlines
🩸 Understanding Hemophilia and the Coagulation Cascade
This paragraph explains hemophilia as a genetic disorder affecting blood clotting, characterized by prolonged bleeding due to impaired hemostasis. It details the normal blood clotting process involving vasoconstriction, platelet plug formation (primary hemostasis), and the coagulation cascade involving clotting factors synthesized by the liver (secondary hemostasis). Hemophilia results from a decrease in clotting factors, leading to less effective secondary hemostasis. The paragraph also describes the extrinsic and intrinsic pathways of the coagulation cascade, which converge on the common pathway to form a stable clot. Hemophilia is often due to deficiencies in factor 8 (hemophilia A) or factor 9 (hemophilia B), and can be caused by liver failure, vitamin K deficiency, or autoimmunity.
🧬 Hemophilia Genetics, Symptoms, and Treatment
This paragraph delves into the genetic aspects of hemophilia, noting that it is an X-linked recessive disorder, typically affecting men due to their single X chromosome. It outlines the symptoms of hemophilia A and B, which are clinically similar, including easy bruising, prolonged bleeding from injuries or surgeries, and internal bleeding such as hemarthrosis. The severity of symptoms is linked to the degree of clotting factor deficiency. Diagnostic methods include lab tests like platelet count, Prothrombin time, and partial thromboplastin time, which help identify the specific clotting factor deficiencies. Treatment usually involves injections of the missing clotting factor, but complications like inhibitors, which are antibodies against the infused factors, can reduce treatment effectiveness. Desmopressin is beneficial for mild hemophilia A, promoting factor 8 stabilization. The paragraph concludes with lifestyle recommendations for individuals with hemophilia to avoid activities and medications that increase bleeding risk.
Mindmap
Keywords
💡Hemophilia
💡Hemostasis
💡Coagulation Cascade
💡Clotting Factors
💡Primary Hemostasis
💡Secondary Hemostasis
💡Extrinsic Pathway
💡Intrinsic Pathway
💡Common Pathway
💡Factor 8 and Factor 9
💡X-linked Recessive
💡Inhibitors
💡Desmopressin (DDAVP)
Highlights
Hemophilia is a genetic disorder characterized by impaired blood clotting, stemming from the Greek words for blood and love, indicating difficulty in stopping bleeding.
Hemostasis, the normal process to stop bleeding, involves vasoconstriction, platelet plug formation, and the coagulation cascade.
The coagulation cascade is initiated by the activation of clotting factors, most of which are proteins synthesized by the liver.
Primary hemostasis is the formation of a platelet plug, while secondary hemostasis involves the reinforcement of this plug with fibrin.
Hemophilia is typically caused by a decrease in clotting factors, leading to less effective secondary hemostasis and increased bleeding.
The coagulation cascade can start through the extrinsic pathway, initiated by tissue factor exposure, or the intrinsic pathway activated by platelets near the injury.
Both pathways converge on the common pathway, which ultimately leads to the formation of a stable clot.
Hemophilia can be caused by insufficient concentration or decreased activity of any coagulation factor except Factor 12 deficiency, which is asymptomatic.
Hemophilia A and B are the most common forms, caused by deficiencies in clotting factors 8 and 9, respectively, and are X-linked recessive disorders.
Von Willebrand disease mimics Hemophilia A and is caused by a deficiency of Von Willebrand factor, affecting primary hemostasis.
Acquired causes of Hemophilia include liver failure, vitamin K deficiency, autoimmunity against clotting factors, and disseminated intravascular coagulation.
Diagnosis of Hemophilia involves lab tests such as platelet count, Prothrombin time, and partial thromboplastin time, which reveal deficiencies in specific clotting factors.
Treatment for Hemophilia A and B involves injections of the missing or non-functional clotting factor, but can be complicated by the development of inhibitors.
Desmopressin (DDAVP) is beneficial for patients with mild Hemophilia A, as it stimulates the release of Von Willebrand factor, stabilizing residual Factor 8.
Individuals with Hemophilia are advised to avoid contact sports and medications that promote bleeding, such as aspirin.
Hemophilia A and B are treated by supplementing the missing clotting factor, with the goal of helping patients maintain a normal life.
Transcripts
foreign
hemophilia is a combination of the Greek
words for blood and love a way of saying
that people with hemophilia love to
bleed or rather that it's hard to stop
bleeding
this is because the process called
hemostasis literally meaning to stop the
flow of blood is impaired
normally after a cut and damage the
endothelium or the inner lining of blood
vessel walls there's an immediate
vasoconstriction or narrowing of the
blood vessel which limits the amount of
blood flow
after that some platelets adhere to the
damaged vessel wall and become activated
and then recruit additional platelets to
form a plug
the formation of the platelet plug is
called primary hemostasis
after that the coagulation Cascade is
activated
first off in the blood there's a set of
clotting factors most of which are
proteins synthesized by the liver and
usually these are inactive and just
floating around in the blood
the coagulation Cascade starts when one
of these proteins gets proteolytically
cleaved this active protein then
proteolytically Cleaves and activates
the next clotting factor and so on
this Cascade has a huge degree of
amplification and takes only a few
minutes from injury to clot formation
the final step is activation of the
protein fibrinogen to fibrin which
deposits and polymerizes to form a
measure on the platelets
so these steps leading up to fibrin
reinforcement of the platelet plug make
up the process called secondary
hemostasis and results in a hard clot at
the site of the injury
in most cases of Hemophilia there's a
decrease in the amount or function of
one or more clotting factors which makes
secondary hemostasis less effective and
allows more bleeding to happen
now that coagulation Cascade can get
started in two ways the first way is
called the extrinsic pathway which
starts when tissue Factor gets exposed
by the injury of the endothelium
tissue Factor turns inactive Factor 7
into activated Factor 7A a for active
and then tissue Factor goes on to bind
the newly formed Factor 7A to form a
complex that turns Factor 10 into active
Factor 10A
Factor 10A with Factor 5A as a cofactor
turns Factor 2 which is also called
prothrombin into Factor 2A also called
thrombin
thrombin then turns Factor 1 or
fibrinogen which is soluble into Factor
1A or fibrin which is insoluble and
precipitates out of the blood at the
site of the injury
thrombin also turns Factor 13 into
Factor 13A which cross-links with fiber
and to form a stable clot
the second way is called the intrinsic
pathway and it starts when platelets
near the blood vessel injury activate
Factor 12 into factor 12a which then
activates Factor 11 to factor 11a which
then activates Factor 9 to factor 9A and
Factor 9A along with Factor 8A work
together to activate Factor 10 to factor
10A
and from that point it follows the same
fate as before
so both the extrinsic and intrinsic
Pathways basically Converge on a single
final path called the common pathway
believe it or not this is a somewhat
simplified version of the coagulation
Cascade but it has all the key parts
needed to understand hemophilia
now an insufficient concentration or
decreased activity of any coagulation
Factor can cause hemophilia except
Factor 12 deficiency which is
asymptomatic
hemophilia usually refers to inherited
deficiencies of coagulation factors
which can be either quantitative or
qualitative
by far the most common of these are
deficiencies of factor 8 which gives
rise to factor 8A and is stabilized by
another Factor called Von Willebrand
factor and this deficiency is called
hemophilia a or classic hemophilia
another common deficiency is deficiency
of factor 9 called hemophilia B which
used to be called Christmas disease
named after the patient who had it not
the holiday
now a mimic of Hemophilia a is Von
Willebrand disease which is an inherited
problem with primary hemostasis caused
by a deficiency of Von Willebrand factor
so in severe Von Willebrand deficiency
factor 8 gets broken down faster and can
become deficient too
as opposed to inherited forms of
Hemophilia one acquired cause of
Hemophilia is liver failure since the
liver synthesizes factors 1 2 5 7 8 9 10
11 and 13.
also vitamin K deficiency can cause
hemophilia since Vitamin K is needed by
the liver to synthesize and release
factors to 7 9 and 10.
another cause is autoimmunity against a
clotting factor and finally there's
disseminated intravascular coagulation
which consumes coagulation factors
now the mutated genes in hemophilia a
are called f8 and in hemophilia B
they're called F9 and these are both on
the X chromosome meaning both conditions
are x-linked recessive so it usually
affects men since they only have one X
chromosome and therefore only one copy
of the f8 and F9 genes
women with one mutated Gene copy have a
remaining healthy copy so they don't get
hemophilia unless X chromosome
inactivation turns off the normal copy
in the majority of cells but generally
women are carriers while men are
symptomatic with the disease
signs and symptoms of Hemophilia A and B
are nearly clinically identical which
makes sense since factors 8A and 9A work
together in the coagulation Cascade to
activate Factor 10.
both of these can cause easy bruising or
echymosis as well as hematomas which are
collections of blood outside the blood
vessels that are often deep in the
muscles
prolonged bleeding after a cut or
surgical procedure for example
circumcision
oozing after tooth extractions
gastrointestinal bleeding hematuria
which is blood in the urine severe
nosebleeds and hemarthrosis or bleeding
into joint spaces
a dangerous complication is bleeding
into the brain which can cause a stroke
or increased intracranial pressure
now the severity of the symptoms depends
on the severity of the underlying
mutation which determines the activity
of the factor
diagnosis of Hemophilia A and B usually
starts with lab tests including a
platelet count which is usually normal a
Prothrombin time and a partial
thromboplastin time
the Prothrombin time tests extrinsic and
common Pathways which means factors 7 10
5 2 which is prothrombin and one which
is fibrinogen
whereas the partial thromboplastin time
test the intrinsic in common Pathways
meaning factors 12 11 9 8 10 5 2 and 1.
since factors 8 and 9 are part of the
intrinsic pathway Prothrombin time is
normal and partial thromboplastin time
is prolonged in hemophilia A and B
in order to confirm hemophilia ARB test
to look at specific Factor activities
and mutation testing of the genes
encoding them can be done
treatment for hemophilia A and B is
usually done with injections of the
missing or non-functional clotting
Factor
unfortunately if the patient has severe
deficiency where intrinsic production of
the factor is absent or very low these
supplemental factors can be seen as
foreign by the immune system which
results in the production of antibodies
that try to eliminate the injected
clotting factors which are called
inhibitors
Inhibitors diminish the treatment's
effectiveness over time and can also
sometimes cause anaphylaxis which is a
severe allergic reaction
for hemophilia a desmopressin also
called ddavp
is helpful for patients with mild
quantitative factor 8 deficiency
desmopressin stimulates Von Willebrand
factor released from endothelial cells
which promotes the stabilization of the
residual Factor 8.
finally it's best for individuals with
hemophilia to avoid contact Sports and
medicines that promote bleeding like
aspirin
all right as a quick recap hemophilia is
a bleeding disorder that's caused by an
impaired coagulation Cascade
hemophilia a is caused by mutations in
the genes for factor 8 and B is caused
by mutations in the genes for factor
nine and these two are the most common
genetic hemophilias and are both treated
by supplementing the missing clotting
Factor
helping current and future clinicians
Focus learn retain and Thrive learn more
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