Coagulation Disorders - Platelet Disorders Overview

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.

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.