Medicine Marrow Pg 171-180 (Hematology)
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Questions and Answers

What does a negative Ristocetin Agglutination Test (RAT) indicate?

  • Deep vein thrombosis
  • HIV infection
  • Bernard-Soulier Syndrome (correct)
  • Hemophilia A

    • Bleeding time is a commonly used test in hematology today.

    False

    What is one of the functions of von Willebrand factor?

    Platelet adhesion

    The __________ curve indicates the absence of the second wave of aggregation with collagen, suggesting a storage pool defect.

    <p>Collagen-deficient</p> Signup and view all the answers

    Match the following platelet aggregation curves with their descriptions:

    <p>Biphasic curve = ADP and epinephrine Monophasic curve = Collagen, arachidonic acid, ristocetin Collagen-deficient curve = Absence of second wave with collagen Ristocetin-normal curve = Normal aggregation with ristocetin</p> Signup and view all the answers

    Which of the following features is inconsistent with Immune Thrombocytopenic Purpura (ITP)?

    <p>Increased platelet count</p> Signup and view all the answers

    Bleeding into joints is a common feature in patients with ITP.

    <p>False</p> Signup and view all the answers

    What is the primary treatment goal for managing ITP?

    <p>Increase platelet count to 30,000/µL</p> Signup and view all the answers

    ITP is classified as __________ if it lasts for more than 12 months.

    <p>chronic</p> Signup and view all the answers

    Match the classification of ITP with its corresponding duration:

    <p>Newly diagnosed = Less than 3 months Persistent = 3 to 12 months Chronic = More than 12 months Duration not specified = Variable duration</p> Signup and view all the answers

    Which of the following is a potential secondary cause of Immune Mediated Thrombocytopenic Purpura (ITP)?

    <p>Rheumatoid Arthritis</p> Signup and view all the answers

    Elderly individuals are commonly affected by Immune Mediated Thrombocytopenic Purpura (ITP).

    <p>False</p> Signup and view all the answers

    What type of immune mechanism is responsible for the destruction of platelets in ITP?

    <p>IgG mediated destruction</p> Signup and view all the answers

    Immune mediated thrombocytopenic purpura is also known as __________ disease.

    <p>Werlhof's</p> Signup and view all the answers

    Match the following conditions with their relation to Immune Mediated Thrombocytopenic Purpura (ITP):

    <p>Primary = Not related to other diseases Secondary = Associated with conditions like SLE and HIV Mucocutaneous bleeding = Common clinical presentation Antibodies = Target Gp IIb/IIIa &amp; Ib/IX</p> Signup and view all the answers

    Which of the following indicates a lack of response to a specific agent in platelet aggregation tests?

    <p>RAT -ve</p> Signup and view all the answers

    A normal aggregation curve can be observed when ristocetin is used.

    <p>True</p> Signup and view all the answers

    What type of defect indicates a positive response to ADP for a storage pool defect?

    <p>Agglutination wave +ve in ADP</p> Signup and view all the answers

    The _____ defect indicates the presence of the primary wave with ADP and epinephrine.

    <p>granule</p> Signup and view all the answers

    Match the following platelet aggregation test results with their corresponding descriptions:

    <p>A: RAT +ve = Aggregation defect B: Aggregation -ve = Indicates absence of aggregation for an agent A: RAT -ve = BSS or VWD B: Agglutination wave +ve = Indicates a positive agglutination response</p> Signup and view all the answers

    Which condition is characterized by a defect in GPIIb-IIIa?

    <p>Glanzmann Thrombasthenia</p> Signup and view all the answers

    Bernard Soulier Syndrome is caused by an autosomal dominant defect.

    <p>False</p> Signup and view all the answers

    What test result is prolonged in Afibrinogenemia?

    <p>Thrombin time</p> Signup and view all the answers

    Patients with Glanzmann Thrombasthenia have a __________ bleeding time.

    <p>prolonged</p> Signup and view all the answers

    Match the following conditions with their characteristic features:

    <p>Glanzmann Thrombasthenia = GPIIb-IIIa defect, RAT+ve Afibrinogenemia = Prolonged thrombin time Bernard Soulier Syndrome = Gp Ib-IX deficiency, RAT-ve Drug-Induced Bleeding = Qualitative platelet disorder</p> Signup and view all the answers

    Which of the following drugs is associated with thrombocytopenia within 24 hours of administration?

    <p>Abciximab</p> Signup and view all the answers

    What is the most common acquired cause of bleeding disorders associated with normal platelet count?

    <p>Uremia bleeding</p> Signup and view all the answers

    Granulation defects are a type of platelet defect.

    <p>True</p> Signup and view all the answers

    Hypersplenism is only associated with bone marrow defects.

    <p>False</p> Signup and view all the answers

    What is indicated by the presence of schistocytes in a peripheral smear?

    <p>It suggests the need to rule out HUS/TTP.</p> Signup and view all the answers

    Name one inherited type of platelet defect.

    <p>Bernard Soulier syndrome or von Willebrand disease</p> Signup and view all the answers

    The __________ test is considered the gold standard in platelet aggregation studies.

    <p>aggregation</p> Signup and view all the answers

    The presence of few __________ on a peripheral smear is considered rare.

    <p>giant platelets</p> Signup and view all the answers

    Match the following drugs with their characteristics:

    <p>Carbamazepine = Anticonvulsant Eptifibatide = GP IIb/IIIa inhibitor Quinine = Associated with drug-induced thrombocytopenia NSAIDs = Can decrease platelet function</p> Signup and view all the answers

    Match the following types of platelet defects with their conditions:

    <p>Gp Ib-IX defect = Bernard Soulier syndrome (BSS) Granule defect = Grey platelet syndrome Gp IIb-IIIa defect = Glanzmann thrombasthenia Afibrinogenemia = Activation/aggregation defects</p> Signup and view all the answers

    What initiates the extrinsic pathway in blood clotting?

    <p>Release of tissue factor from damaged tissues</p> Signup and view all the answers

    Fibrinolysis is the process of forming blood clots.

    <p>False</p> Signup and view all the answers

    What is the role of thrombin in the clotting cascade?

    <p>Thrombin converts fibrinogen to fibrin.</p> Signup and view all the answers

    The common pathway is activated when factor X (from either the ________ or ________ pathway) is activated.

    <p>intrinsic, extrinsic</p> Signup and view all the answers

    Match the pathways with their triggers:

    <p>Intrinsic pathway = Activation of Factor XII Extrinsic pathway = Release of tissue factor Common pathway = Activation of Factor X Fibrinolysis = Activation of plasminogen</p> Signup and view all the answers

    Which type of bleeding is associated with platelet-related disorders?

    <p>Mucosal bleeding</p> Signup and view all the answers

    Male patients are more likely to experience coagulation-related bleeding compared to female patients.

    <p>False</p> Signup and view all the answers

    What type of bleeding occurs immediately after trauma?

    <p>Platelet-related bleeding</p> Signup and view all the answers

    The classification for bleeding disorders involving a single lineage is referred to as __________ bleeding.

    <p>primary platelet</p> Signup and view all the answers

    Match the types of bleeding to their respective causes:

    <p>Mucosal bleeding = Platelet-related Petechiae = Platelet-related Delayed bleeding = Coagulation-related Joint bleeding = Coagulation-related</p> Signup and view all the answers

    What role does the endothelium play in platelet adhesion?

    <p>It acts as an antithrombotic barrier.</p> Signup and view all the answers

    Heparin-like molecules bind with AT-III to inactivate factors II, IX, X, XI, and XII.

    <p>True</p> Signup and view all the answers

    Name one substance released from δ granules during platelet activation.

    <p>ADP</p> Signup and view all the answers

    The platelet receptor Gp IIb – IIIa is involved in binding to __________ during aggregation.

    <p>fibrinogen</p> Signup and view all the answers

    Match the following antiplatelet or anticoagulant substances with their functions:

    <p>PGI₂ = Antiplatelet agent Thrombomodulin = Activates protein C Heparin-like molecules = Inactivates clotting factors Tissue factor pathway inhibitor (TFPI) = Inactivates VII &amp; X</p> Signup and view all the answers

    Study Notes

    Ristocetin Agglutination Test (RAT)

    • Used to assess platelet adhesion.
    • Negative result may indicate Bernard-Soulier Syndrome (BSS) or Von Willebrand Disease (VWD).
    • If negative, check activated partial thromboplastin time (APTT) to evaluate intrinsic pathway defects.

    Bleeding Time

    • An obsolete test.
    • Von Willebrand factor's function:
      • Platelet adhesion
      • Transports factor VIII

    Platelet Aggregation Curves

    • Biphasic curve: Observed with ADP and epinephrine.
    • Monophasic curve: Seen with collagen, arachidonic acid, and ristocetin.
    • Collagen-deficient curve: Suggests storage pool defect.
      • Features: Absence of the second wave of aggregation with collagen, normal ristocetin aggregation.
    • Ristocetin-normal curve: Indicative of normal aggregation with ristocetin.
      • Associated with granule defects in certain conditions.

    Immune Mediated Thrombocytopenic Purpura (ITP)

    • Also known as Werlhof's disease.
    • Not seen in elderly individuals.

    Causes

    • Primary
    • Secondary:
      • Systemic lupus erythematosus (SLE)
      • Rheumatoid arthritis (RA)
      • Helicobacter pylori (H. pylori)
      • Human immunodeficiency virus (HIV)
      • Hepatitis C virus (HCV)

    Pathogenesis

    • Immune (IgG) mediated destruction of platelets.
      • Antibodies against Gp IIb/IIIa & Ib/IX.
    • Inhibition of platelet release from megakaryocytes.

    Clinical Presentations

    • Mucocutaneous bleeding.
    • Low platelet count.

    Features Inconsistent with ITP

    • Fever
    • Pallor
    • Jaundice
    • Subconjunctival hemorrhage
    • Bleeding into joints
    • Splenomegaly
    • Lymphadenopathy
    • Predominant giant platelets
    • Red cell morphological abnormality
    • WBC abnormality

    Classification

    • Duration:
      • 1 year
      • Newly diagnosed
      • Persistent
      • Chronic

    Treatment

    • Goal: Increase platelet count to 30,000/µL to prevent bleeding.
    • If platelet count:

      • 30,000: Wait and watch

      • <30,000: Treatment options:
        • First-line: Corticosteroids
        • Second-line: Immunoglobulins
        • Third-line: Splenectomy

    Approach to Bleeding Disorders

    • Platelet Aggregation Tests:
      • Used to diagnose platelet function disorders.
      • Focus on platelet aggregation curves and detection of defects.
    • ADP Deficient and Collagen Deficient platelet aggregation curves: Presented in the document.
    • Ristocetin: Normal
      • Normal aggregation curve when ristocetin is used.
      • Indicates a granule defect.
    • Optical Density Test:
      • Normal agglutination/adhesion: Indicated by a normal optical density.
      • Aggregation defect:
        • A: RAT +ve: Indicated by the aggregation curve for a specific agent.
        • B: Aggregation -ve: Indicates the absence of aggregation for a given agent in a specific test.
    • BSS or VWD:
      • A: RAT -ve: Indicates a lack of response to a specific agent.
      • B: Agglutination wave +ve: Indicates a positive response and a specific type of agglutination for a given agent in the test.
    • Storage pool defect/granule defect:
      • A: Agglutination wave +ve in ADP: Indicates a positive response to ADP for a storage pool defect or granule defect.

    Key Takeaways

    • Different types of platelet aggregation defects, including granule defects, storage pool defects, and aggregation defects.
    • Graphs and descriptions show how these defects affect platelet aggregation curves and how different agonists and tests showcase these impairments.
    • Visual interpretation of aggregation curves is essential for diagnosis.

    Hematology - Platelet Disorders

    Glanzmann Thrombasthenia

    • Autosomal recessive inheritance.
    • Normal thrombin time.
    • GPIIb-IIIa defect (Fibrinogen receptor lost).
    • RAT +ve.
    • Normal platelet count.
    • Prolonged bleeding time.
    • Recurrent episodes of bleeding and heavy menstrual bleeding.

    Afibrinogenemia

    • Prolonged thrombin time.

    Bernard Soulier Syndrome

    • Autosomal recessive inheritance.
    • Deficiency of Gp Ib-IX.
    • RAT negative.
      • Adhesion defect.

    Peripheral Smear Findings

    • Megathrombocytosis and mild thrombocytopenia.

    Drug-Induced Bleeding (Qualitative)

    • Aspirin
    • Beta-Lactams
    • Dipyridamole/Theophylline
    • Ticlopidine/Clopidogrel
    • Dextran

    Anticonvulsants

    • Carbamazepine
    • Phenytoin
    • Valproate

    GP IIb/IIIa Inhibitors

    • Abciximab: Thrombocytopenia within 24 hours.
    • Eptifibatide
    • Tirofiban

    Drugs

    • NSAIDs
    • Quinine
    • Penicillin

    Mechanism

    • Drug-specific antibody
    • Induce antibody formation
    • Hapten-dependent antibody

    Rule Out Hypersplenism

    • Hypersplenism due to platelet sequestration: Seen in liver disease.
      • Low platelet count
      • Bone marrow defect
      • Lack of platelet, RBC, WBC formation
      • Platelet destruction
      • Sequestration of platelets

    Peripheral Smear

    • Presence of schistocytes: Rule out HUS/TTP.
    • Normal smear.
    • Presence of few giant platelets (Rare).

    Summary

    • Platelet-type bleeding (Corresponding to platelet count).
    • Single lineage disorders: RBC, WBC → Normal.
    • Not drug-induced.
    • No hypersplenism.
    • Peripheral smear: Normal.
    • ITP (Immune thrombocytopenic purpura).

    Clotting Cascade

    • Series of biochemical reactions leading to blood clot formation.

    Intrinsic Cascade (In Vitro)

    • Starts with activation of factor XII.
    • Proceeds through factors IX, VIII, XI, and X.
    • Triggered by high molecular weight kininogen, Kallikrein, and activation of factor XII.
    • Leads to activation of factor X, which participates in the common pathway.

    Extrinsic Cascade (In Vivo)

    • Begins with tissue factor (thromboplastin) release from damaged tissues.
    • Triggered by:
      • Endothelial injury
      • Tissue factor (thromboplastin)
      • Factor VII
      • Factor X
    • Leads to activation of factor X, which then participates in the common pathway.

    Common Cascade

    • Activated when factor X (from either the intrinsic or extrinsic pathway) is activated.
    • Factor X activates prothrombin (factor II) to thrombin (factor IIa).
    • Thrombin converts fibrinogen to fibrin.
    • Fibrin forms a clot.
    • Factor XIII stabilizes the fibrin clot.

    Fibrinolysis

    • Process of dissolving blood clots.
    • Tissue plasminogen activators (tPA) activate plasminogen to plasmin.
    • Plasmin degrades fibrin.
    • t-PA inhibitors (Antifibrinolytics), TAFI, and plasminogen activator inhibitor (PAI) regulate fibrinolysis.

    Tests

    • APTT: Measures intrinsic and common cascade.
      • Low APTT values may indicate poor sensitivity.
    • PT: Measures extrinsic and common cascade.

    Approach to Bleeding Disorders

    Qualitative Disorder of Platelets

    • Presence of bleeding with a normal platelet count.

    Causes

    • Acquired:

      • Uremia bleeding (Most common cause).
      • Drugs.

    • Inherited:

    Types of Platelet Defects

    1. Platelet adhesion defects:
      • Gp Ib-IX defect: Bernard Soulier syndrome (BSS)
      • von Willebrand disease (vWD)
    2. Granulation defects:
      • Granule defect: Grey platelet.
      • Granule defect: Hermansky-Pudlak syndrome.
    3. Activation/aggregation defects:
      • Gp IIb-IIIa defect: Glanzmann thrombasthenia.
      • Afibrinogenemia.

    Investigations

    1. Platelet function analyzer (PFA-100):
      • Screening test.
      • Aperture closure time: Prolonged (>80 sec) → Function disorder.
    2. Aggregation test:
      • Gold standard
      • Shows wave of aggregation on adding agent
        • Weak agents (ADP, epinephrine):
          • Two waves:
            • a. Primary aggregation: Directly induces aggregation (No release of granules).
            • b. Secondary aggregation: Release of thromboxane A2 or ADP from granules.
        • All other agents:
          • Single wave

    Second Line: In Relapse

    • Rituximab + Dexamethasone
    • Thrombopoietin analogues, Eltrombopag (oral), Romiplostim (s/c)
    • Splenectomy (complication)
    • Azathioprine

    Follow Up

    • Rise in counts: 2-4 days

    Platelet Cascade

    1. Adhesion

    • Role of endothelium:

      • Endothelial injury is necessary for platelet adhesion.
      • Subendothelium is prothrombotic since endothelium is antithrombotic.
      • a. Antiplatelet: PGI₂, nitric oxide, ADPase.
      • b. Anticoagulant:
        • Heparin-like molecules → Bind with AT-III → Inactivates II, IX, X, XI, XII.
        • Thrombomodulin → Binds to thrombin → Activates protein C → Inactivates V & VIII.
        • Tissue factor pathway inhibitor (TFPI) → Inactivates VII & X (Tissue factor: II).
      • c. Fibrinolysis: Release of tissue plasminogen activator (TPA)

    • Mechanism:

      • Source:
        • Megakaryocyte
        • Endothelium:
          • Coiled form
          • In Weibel-Palade granules.
      • Receptors:
        • Gp VI on collagen.
        • Gp Ib-IX on platelets.

    2. Activation/Degranulation

    • Activation through degranulation.
      • a granules
      • δ granules (dense) → ADP > ATP, calcium, histamine, serotonin.

    3. Aggregation

    • Gp IIb – IIIa
    • Fibrinogen: Bind to platelets

    Protocol for Evaluation

    Platelet Coagulation
    Onset of bleeding Immediately after trauma
    Type of bleeding Mucosal bleeding (e.g., gum bleed, epistaxis, menorrhagia, intra-operative bleeding), Petechiae (<10 mm)
    Sex Male = Female

    2. Lineage

    Single Lineage Trilineage
    1° platelet bleeding Leukemia, Aplastic anemia, MDS

    • Note:*

    • Based on platelet count:

      • 20,000/µL: No bleeding O/E

      • <20,000/µL: Bleeding O/E
      • <10,000/µL: Risk of spontaneous bleeding

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    Description

    This quiz focuses on key hematological tests related to platelet function, including the Ristocetin Agglutination Test and bleeding time. Understand the significance of platelet aggregation curves and their implications in various disorders such as Bernard-Soulier Syndrome and Immune Mediated Thrombocytopenic Purpura. Test your knowledge and comprehension of these vital laboratory assessments!

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