Platelet Disorders and Treatments Quiz

Course Information

• Course Title: Clinical Laboratory Sciences, M.Sc.
• Course Code: MCLS7211
• Topic: Blood Homeostasis and Coagulation
• Semester: First Semester, 2024/2025
• Lecturer: Dr. Ola Karmi
• Email: [email protected]

Lecture 11: Platelet Disorders

Coagulation Cascade and Fibrinolysis

• Coagulation, anticoagulation, and fibrinolysis work together to maintain a balance.
• The coagulation cascade involves a series of protein activation steps leading to clot formation.
• TFPI, tissue factor pathway inhibitor, and APC, activated protein C, regulate coagulation.
• Antithrombin (AT) inhibits thrombin.
• Thrombin converts fibrinogen to fibrin, forming the clot.
• Fibrinolysis is the breakdown of fibrin clots by plasmin.

Platelets

• Platelets adhere to vessel walls when intact endothelium is damaged to stop bleeding.
• They plug ruptures in blood vessel walls.
• They provide a surface for promoting blood coagulation.

Thrombocytopenia

• A condition in which the platelet count is abnormally low, typically below 100x10⁹/L.
• Clinical symptoms generally appear when the platelet count falls below 50 and severe or spontaneous bleeding occurs when the count is <10.
• Bleeding risk is inversely proportional to the platelet count.
• Causes include production abnormalities (marrow damage, aplasia), abnormal distribution (splenomegaly, liver disease, myelofibrosis), or immune or non-immune destruction.

Thrombocytopenia- Non-Inherited: Drugs and Chemical Agents

• Maternal use of drugs and chemical agents can cause thrombocytopenia.
• This may involve direct damage to platelets or production suppression.
• Some drugs can cause the formation of antibodies that target platelets, which are then destroyed.
• These drugs (ethanol, alkylating agents, anti-metabolites) can cross the placenta and affect newborns.
• Usually remits quickly, with minimal severe/fatal hemorrhages.

Thrombocytopenia- Non-Inherited: Isoimmune Thrombocytopenia

• Platelet antibodies (IgG) produced by the mother during active immunization by the fetus can affect the fetus.
• Mothers who are PIA1-negative and fetuses PIA1-positive are at higher risk.
• Newborns may have petechiae, purpura or severe bleeding at birth or weeks later.
• Platelet count recovers within a month, but severe/fatal intracranial hemorrhages can occur.

Thrombocytopenia- Non-Inherited: Infiltration of Bone Marrow

• Rare and limited to disseminated reticuloendotheliosis and congenital leukemia.
• Possible thrombocytopenia with myeloid and erythroid depression.
• Possible infiltration disorders like lymphoma and myelofibrosis in children.

Thrombocytopenia- Non-Inherited: Infections

• Infections with microorganisms such as toxoplasma, CMV, Rubella, herpesviruses, and hepatitis can cause thrombocytopenia.
• This can be mild in some cases but severe in newborns.
• The process can involve viral infections, invasion of megakaryocytes or destruction of circulating platelets.

Thrombocytopenia- Non-Inherited: Other Causes

• Congenital thrombocytopenic purpura in children whose mothers have idiopathic thrombocytopenic purpura.
• Increased platelet consumption or destruction, such as cases of lupus erythematosus or other autoimmune diseases.
• Immune-mediated destruction may cause platelets to survive for a short time (minutes to 2-3 days).

Inherited Thrombocytopenias

• Several inherited disorders may lead to thrombocytopenia due to generalized bone marrow failure (e.g., Fanconi anemia).

Platelet Structures and Disorders

• Detailed diagrams and tables discuss various platelet structures, their functions, and relevant inherited disorders.

Therapy

• Treatment for conditions like congenital thrombocytopenia may include washed maternal platelets, corticosteroids, or exchange transfusion for severe cases.
• Splenectomy can be effective for some patients.
• Educating patients about preventing trauma and practicing regular dental care is vital.
• Antifibrinolytic agents, desmopressin (DDAVP), and recombinant factor VIIa can help manage mild to moderate bleeding.
• Synthetic thrombopoietin agonists are also used.
• Allogenic bone marrow transplantation may cure some inherited disorders.

Lab Evaluation

• Various lab tests, including platelet count, bleeding time (PT), activated partial thromboplastin time (APTT), and platelet function tests, help diagnose platelet disorders.
• Specific test results are included in tables depending on the suspected disorder.

Disorders of Platelet Function

• Different aspects of platelet function (adhesion, signaling, aggregation) and related inherited disorders are discussed.
• Detailed diagrams and tables provide clear and comprehensive descriptions of the disorders and their effects on platelet function.

Glanzmann's Thrombasthenia

• Characterized by a deficiency or defect in the platelet glycoprotein IIb/IIIa complex.
• This leads to impaired platelet aggregation and prolonged bleeding time.
• Diagnosis involves assessing platelet aggregation in response to agonists like ADP and collagen.
• Qualitative and quantitative assessment of the GPIIb/IIIa receptor is also part of the diagnosis.

Classification of Inherited Platelet Disorders

• A table is included classifying different inherited platelet disorders based on observed defects and associated characteristics.

Test your knowledge on platelet disorders, their causes, and treatment options in this comprehensive quiz. Explore key concepts like primary and secondary aggregating agents, and the role of integrins in platelet aggregation. Perfect for students and professionals in hematology or medical fields.