coagulation disorders Flashcards
name Acquired Platelet Disorders
- Immune thrombocytopenia (ITP)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Disseminated intravascular coagulation (DIC)
- Drug-induced platelet dysfunction
- Myeloproliferative disorders (MPD)
- Chronic renal failure
name inherited Platelet Disorders
- Glanzmann’s Thrombasthenia
- Bernard-Soulier Syndrome
- Storage Pool Diseases
Glanzmann’s Thrombasthenia Background
Glanzmann’s Thrombasthenia was first identified in
1918 by Eduard Glanzmann, a Swiss paediatrician.
* One of the first patients was a 7-year-old girl with normal
platelet count but very large bruises on her body.
* Affects 1 person in 1 million.
* Autosomal recessive disease caused by mutations in the
genes ITGA2B and ITGB3.
* Leads to severe copy number reduction or reduced
function of the fibrinogen receptor Integrin αIIbβ3 (aka
GPIIbGPIIIa complex).
* Platelets will fail to bind to each other, and the platelet
plug cannot be stabilised by fibrinogen.
Glanzmann’s Thrombasthenia Diagnosis and Treatment
Bernard-Soulier Syndrome Background
Bernard-Soulier Syndrome Diagnosis and Treatment
Most often identified in very young individuals, in mild disease forms the
patient is older.
* Severe bruising and bleeding.
* Platelet count: 10-100 x 109
/L (reference interval is 150-400 x 109
/L)
* Lumi-aggregometry test: Low response to ristocetin, sometimes also
thrombin.
* Flow cytometry test: Decreased levels of receptors in the GPIb-IX-V
complex.
* Genetic test: Mutations in GPIBA, GPIBB or GP9.
* Treatment: Platelet transfusion (NovoSeven® not approved yet).
* Other support: Hormonal treatment in women and iron supplements for
blood loss. Pressure on bleeding site if possible, use of antifibrinolytic
substances applied topically.
What does severe bleeding mean?
- Large bruising from little or no damage.
- Spontaneous bleeding from the gums.
- Very heavy periods, can last a month (menorrhagia, >7 days).(some report up to 10 bleeding episodes a week)
- Nosebleeds that can last for more than a day (epistaxis).
- Potential death from trauma to the head (intracranial bleeding).
- Bleeding into joints that reduces mobility and causes pain.
- Major effects on everyday life!
- Not everyone cannot attend sports like most people, a small
injury could become dangerous. - Sometimes avoid social situations due to bleeds.
- Surgeries and giving birth has increased risks of severe bleeds.
Idiopathic Thrombocytopenic Purpura (ITP)
- Idiopathic Thrombocytopenic Purpura (ITP) is
acquired thrombocytopenia, also known as Immune
Thrombocytopenia. - Platelets are destroyed by the body’s immune system
- Primary: Autoimmune anti-platelet antibodies.
- Secondary: Other autoimmune diseases or
infections by bacteria or viruses. - Affects 4 in 100.000 people per year.
- Leads to a reduction in platelet count that results in
bleeding. - Requires <100 x 109
/L for diagnosis. - Significant bleeding at <10 x 109
/L. - Treatment: Steroids (reduce antibody production) to
slow down platelet destruction or Intravenous gamma
globulin (neutralisation)
Thrombocytopenic Thrombotic Purpura
- Thrombocytopenic Thrombotic Purpura (TTP) is
haemolytic condition. - Platelets are clumping together in small vessels leading
to thrombocytopenia – can be deadly. - Low levels or decreased function of ADAMTS13 a
small enzyme that comes from the endothelial cells. - ADAMTS13 cleaves von Willebrand Factor into
smaller less active fragments. - Autoimmune pathogenesis - antibodies forming
against ADAMTS13. - Affects up to 11 in 1 million.
- Treatment: Plasma exchange – healthy plasma with
ADAMTS13 and removal of antibodies
Disseminated intravascular coagulation (DIC)
- Disseminated intravascular coagulation (DIC) is
severe thrombotic condition leading to blood clots, can
lead to multi-organ dysfunction and death. - Caused by increase in Tissue Factor being released from
into circulation from endothelial cells leading to activation
of the extrinsic pathway. - Pathogenesis often involves severe sepsis or cancer.
- Platelets and coagulation factors are consumed during
DIC which then leads to uncontrollable bleeding. - Affects up to 1% of patients admitted to hospital.
- Treatment:
- Low platelet count and bleeding: Platelet concentrate
or blood transfusion. - Thrombosis or risk of thrombosis: Low molecular
weight heparin as prophylaxis
Drug-induced platelet dysfunction
- Aspirin is a common drug used to prevent the
formation of blood clots. - Non-steroid anti-inflammatory drugs (NSAIDs)
like ibuprofen are common drugs for pain relief that
also affect platelets - Aspirin (irreversible) and NSAIDs (reversible)
blocks the function of cyclooxygenase-1 (COX-1). - COX-1-inhibition prevents the generation of
Thromboxane A2 in platelets – an important
secondary mediator. - Prolongs bleeding time, the body needs to make
new platelets to go back to normal.
Thrombophilia
Thrombophilia is an abnormal tendency to form
blood clots.
* Often identified in individuals after a deep vein
thrombosis (DVT) has occurred.
* Have an increased risk for pulmonary embolism
(PE).
- Formation of a DVT:
1. Enhanced coagulation.
2. Changes to blood flow causing local hypoxia.
3. Damage to the vessel wall which starts
coagulation.
Name Inrited Thrombophilia
- Protein C deficiency
- Protein S deficiency
- Factor V Leiden
- Antithrombin deficiency
- Prothrombin G20210A variant
Name Acquired Thrombophilia
Antiphospholipid syndrome
* Postoperative venous thrombosis
* Malignancy
* Surgery/Pregnancy/Oral Contraceptive
Explain protein C Deficiency
- Protein C Deficiency is an autosomal dominant
condition. - Affects 1 in 200 to 1 in 500 individuals.
- Protein C is activated by thrombin.
- Activated Protein C cleaves Factor Va and Factor
VIIIa to inactivated products which leads to less
thrombin formation.
Protein C Deficiency - Requires Protein S as a co-factor to
cause inactivation of Factor Va and
Factor VIIIa. - Deficiency in Protein C removes one
of the brakes on coagulation which
promotes clotting
