Coagulation Disorders - Platelet Disorders Overview

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Questions and Answers

What is one example of an inherited platelet disorder?

Drug-induced platelet dysfunction

Chronic renal failure

Myeloproliferative disorders

Glanzmann’s Thrombasthenia (correct)

Which of the following is an acquired platelet disorder?

GATA1 mutations

Bernard-Soulier Syndrome

Immune thrombocytopenia (ITP) (correct)

Storage Pool Diseases

What is a distinguishing feature of inherited platelet disorders?

They do not have a genetic basis.

They are only caused by environmental factors.

They primarily affect platelet function.

They always affect platelet numbers. (correct)

Which coud contribute to drug-induced platelet dysfunction?

Specific medication interactions Signup and view all the answers

Which disorder is characterized by a deficiency in ADAMTS13?

Thrombotic Thrombocytopenic Purpura (TTP) Signup and view all the answers

What can be the effect of Glanzmann’s Thrombasthenia on patients?

Excessive bleeding. Signup and view all the answers

Which of the following is NOT a treatment typically available to patients with platelet disorders?

Surgery Signup and view all the answers

What does severe bleeding NOT include?

Mild nosebleeds that resolve quickly Signup and view all the answers

Which of the following describes Idiopathic Thrombocytopenic Purpura (ITP)?

Resulting from the body's immune system destroying platelets Signup and view all the answers

What is a potential major effect of severe bleeding on a patient’s daily life?

Impaired mobility due to bleeding into joints Signup and view all the answers

Which of the following can be a symptom of severe bleeding?

Bleeding episodes occurring multiple times a week Signup and view all the answers

What is the primary genetic cause of Glanzmann’s Thrombasthenia?

Mutations in ITGA2B and ITGB3 Signup and view all the answers

Which test would show no visible platelet aggregation in a patient with Glanzmann’s Thrombasthenia?

Lumi-aggregometry test Signup and view all the answers

What is a notable symptom of Bernard-Soulier Syndrome?

Giant platelets and thrombocytopenia Signup and view all the answers

What does the flow cytometry test reveal in patients with Bernard-Soulier Syndrome?

Decreased levels of GPIb-IX-V complex receptors Signup and view all the answers

Which treatment is approved for Glanzmann’s Thrombasthenia during severe bleeding?

NovoSeven® Signup and view all the answers

What is the approximate platelet count range in patients with Bernard-Soulier Syndrome?

10-100 x 10^9/L Signup and view all the answers

Which genetic mutations cause Bernard-Soulier Syndrome?

Mutations in GPIBA, GPIBB, and GP9 Signup and view all the answers

What condition is characterized by severe bruising and bleeding with normal platelet count?

Glanzmann’s Thrombasthenia Signup and view all the answers

In Glanzmann's Thrombasthenia, how do platelets behave due to the condition?

Platelets fail to bind to each other Signup and view all the answers

What other support is provided for women suffering from Glanzmann's Thrombasthenia?

Hormonal treatment Signup and view all the answers

Study Notes

Coagulation Disorders - Part I: Platelet Disorders

Platelet disorders are categorized as inherited or acquired.
Aims of this lecture: Understand platelet disorders' pathology and available treatments.
Required preparation: Review previous haemostasis lectures (parts I, II, and III).
Inherited platelet disorders include: Glanzmann's Thrombasthenia, Bernard-Soulier Syndrome, and Storage Pool Diseases.
Acquired platelet disorders include: Immune thrombocytopenia (ITP), Thrombotic Thrombocytopenic Purpura (TTP), Disseminated intravascular coagulation (DIC), Drug-induced platelet dysfunction, Myeloproliferative disorders (MPD), and Chronic renal failure.

Glanzmann's Thrombasthenia Background

Discovered in 1918 by Eduard Glanzmann.
Characterized by a 7-year-old girl with extensive bruising despite a normal platelet count.
Affects approximately 1 in 1 million people.
An autosomal recessive disorder caused by mutations in the ITGA2B and ITGB3 genes.
Leads to reduced or absent function of the fibrinogen receptor Integrin αIIbb3 (GPIIb-IIIa).
Platelets fail to adhere to each other, compromising platelet plug formation.

Glanzmann's Thrombasthenia Diagnosis and Treatment

Typically diagnosed in young individuals with spontaneous bruising and bleeding.
Platelet count: Normal.
Lumi-aggregometry: Absence of platelet aggregation.
Flow cytometry: Lack of Integrin αIIbb3.
Genetic testing: Identifies mutations in ITGA2B and ITGB3.
Treatment: Platelet transfusions to reduce mortality during severe bleeding; hormonal treatment for women and iron supplements for blood loss.
Early identification and treatment are critical for preventing severe complications.

Bernard-Soulier Syndrome Background

Discovered in 1948 by Jean Bernard and Jean Pierre Soulier.
Characterized by a male patient with chronic bleeding, who died at age 28.
Affects approximately 1 in 1 million people.
An autosomal recessive disorder caused by mutations in the GP1BA, GP1BB, and GP9 genes.
Leads to reduced or dysfunctional GPIb-IX-V complex, a crucial receptor for von Willebrand Factor (vWF).
Characterized by thrombocytopenia and giant platelets.

Bernard-Soulier Syndrome Diagnosis and Treatment

Typically, diagnosed in young individuals with severe bruising and bleeding.
Platelet count: Low (10-100 x 10⁹/L).
Lumi-aggregometry: Reduced ristocetin-induced aggregation.
Flow cytometry test: Reduced or absent expression of GPIb-IX-V receptors.
Genetic analysis identifies mutations in GP1BA, GP1BB, or GP9.
Treatment: Platelet transfusions (NovoSeven® not yet approved). Other supportive care includes hormonal treatment for women and iron supplements for anemia, localized pressure on bleeding sites, and antifibrinolytic substances.

Idiopathic Thrombocytopenic Purpura (ITP)

ITP is acquired thrombocytopenia.
Platelets are destroyed by the immune system's anti-platelet antibodies (primary) or by other autoimmune diseases/infections (secondary).
Affects approximately 4 in 100,000 people annually.
Characterized by bleeding disorders and platelet count below 100 x 10⁹/L for diagnosis.
Can progress to severe bleeding with platelet counts below 10 x 10⁹/L.
Treatment options include steroids, intravenous gamma globulin, and/or splenectomy to address underlying immune response.

Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a rare, potentially life-threatening condition.
Characterized by platelet clumping (thrombocytopaenia) and blood vessel damage (haemolytic condition) in small blood vessels.
Often stems from a lack of ADAMTS13 enzyme activity that leads to impaired breakdown of von Willebrand Factor (vWF).
Symptoms include thrombocytopenia and microangiopathic hemolytic anaemia.
Diagnosis often includes finding low levels of ADAMTS13 enzyme and the presence of antibodies against ADAMTS13.
Treatment typically involves plasma exchange to rapidly replace ADAMTS13 and reduce the amount of vWF in circulation.

Disseminated Intravascular Coagulation (DIC)

DIC is a serious condition causing widespread blood clots, often involving immune or cancer-related events that initiate the extrinsic pathway.
Symptoms include bleeding due to consumption of platelets and clotting factors, and multiple organ dysfunction from blocked blood vessels.
Can be triggered by severe infections, cancers, or obstetric complications.
Diagnosis involves low platelet count, high fibrin degradation products (FDP), prolonged clotting times, and signs of organ damage.
Treatment includes addressing the underlying cause, blood transfusions for low platelet counts or bleeding, and low-molecular-weight heparin for thrombosis symptoms.

Drug-Induced Platelet Dysfunction

Medications, such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), can interfere with platelet function by inhibiting COX-1 enzyme, reducing thromboxane A2 production.
This typically leads to prolonged bleeding time.
This should be considered during treatment planning for other conditions.

Inherited and Acquired Platelet Disorders Summary

Platelet disorders encompass conditions with inherited or acquired causes, characterized by different genetic mechanisms and clinical presentations, impacting diagnosis and treatment strategies.

Summary of Bleeding Symptoms

Large bruising without trauma
Spontaneous bleeding from gums
Heavy menstruation (menorrhagia)
Frequent nosebleeds (epistaxis)
Bleeding into joints causing pain and reduced mobility
Intracranial bleeding, a serious risk
Overall, severely impacts daily activities and increases surgical and childbirth risks.

Other Inherited Platelet Disorders

Storage pool diseases, characterized by abnormal platelet granules and defective storage of related factors and secretion.
Note the wide range of possible causes and impacts on patients.

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Description

This quiz covers the key concepts of platelet disorders, including both inherited and acquired types. Participants will explore the pathologies and treatments associated with conditions such as Glanzmann's Thrombasthenia and Immune Thrombocytopenia. A review of prior haemostasis lectures is recommended for better understanding.