Free ASCP MLS Exam Practice Questions Mock Test: Part 39 – Platelet Disorders (Quantitative & Functional Defects)

• Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that irreversibly acetylates and inhibits cyclooxygenase-1 (COX-1) in platelets.

• Since platelets are anucleated and cannot synthesize new proteins, this inhibition lasts for the entire lifespan of the platelet (7-10 days).

The other options work differently:

• a) Warfarin: Inhibits vitamin K-dependent synthesis of coagulation factors (II, VII, IX, X) in the liver. It does not directly affect platelet function.

• b) Heparin: Potentiates the action of antithrombin III to inhibit thrombin and other coagulation factors (mainly Xa). It does not directly affect platelet function.

• d) Streptokinase: A thrombolytic (fibrinolytic) agent that activates plasminogen to plasmin to break down blood clots. It does not inhibit platelet function.

While all the listed options can cause bleeding, thrombocytopenia (a low platelet count) is by far the most common underlying cause of clinically significant bleeding. This is because platelets are essential for the initial formation of a hemostatic plug at the site of vessel injury.

• a) Qualitative platelet defect: These inherited or acquired disorders (e.g., von Willebrand disease, aspirin effect) are less common than simple thrombocytopenia.

• b) Qualitative abnormality of fibrinogen (Dysfibrinogenemia): This is a very rare disorder.

• c) Quantitative abnormality of fibrinogen (Hypofibrinogenemia/Afibrinogenemia): This is also a very rare disorder.

• May-Hegglin anomaly is a rare, inherited autosomal dominant disorder caused by a mutation in the MYH9 gene. Its classic triad of findings includes:

  1. Giant platelets

  2. Döhle-like inclusions in the cytoplasm of white blood cells (neutrophils). These are aggregates of non-functioning ribosomal RNA.

  3. Thrombocytopenia (low platelet count)

The other options are incorrect:

• a) Microcytic anemia: This is not a feature of May-Hegglin anomaly.

• c) Hemolysis: This is not associated with the anomaly.

• d) Hypersegmented neutrophils: This is characteristic of megaloblastic anemias (e.g., B12 or folate deficiency), not May-Hegglin.

• Pseudothrombocytopenia is a falsely low platelet count reported by an automated analyzer with a normal actual platelet count in the patient’s body.

• The most common cause is EDTA-dependent platelet clumping, where antibodies cause platelets to aggregate in vitro (in the test tube) in blood samples collected in the anticoagulant EDTA. These clumps are too large to be counted as individual platelets by the analyzer, leading to a spurious low count. This can be confirmed by examining a peripheral smear or re-drawing the sample in a different anticoagulant like citrate.

The other options cause true thrombocytopenia:

• b) Bone marrow failure: Leads to decreased platelet production.

• c) Splenomegaly: Leads to increased platelet sequestration.

• d) Increased platelet destruction: As seen in ITP or DIC.

• Platelet satellitism is a phenomenon where platelets clump around neutrophils (or other white blood cells) in vitro, usually due to an EDTA-dependent antibody.

• These clumps are too large to be counted as individual platelets by the automated analyzer, resulting in a falsely low reported platelet count.

• However, on the peripheral smear, an adequate number of platelets is visible, often seen in these characteristic rosettes.

The other options can also cause pseudothrombocytopenia but are less common or direct than satellitism:

• b) Giant platelets: While very large platelets may be excluded from the count by some analyzers, this would be a true thrombocytopenia, not a false one. The smear would show the giant platelets.

• c) Microcytic red blood cells: This would not cause a falsely low platelet count.

• d) Cryoglobulinemia: Can cause clumping that leads to pseudothrombocytopenia, but platelet satellitism is the more classic and specific cause for this presentation.

• Von Willebrand factor (vWF) is synthesized in two cell types:

  1. Endothelial cells (the primary site of synthesis)

  2. Megakaryocytes

• In megakaryocytes, vWF is packaged into platelet alpha-granules and is released upon platelet activation.

The other options are incorrect:

• a) Myeloblasts: Give rise to granulocytes and do not synthesize vWF.

• b) Monoblasts: Give rise to monocytes/macrophages and do not synthesize vWF.

• c) Lymphoblasts: Give rise to lymphocytes and do not synthesize vWF.

• Platelet Disorders (e.g., ITP, Bernard-Soulier): Cause defects in primary hemostasis (the initial formation of the platelet plug). This leads to bleeding from small vessels, manifesting as:

  • Petechiae (pinpoint skin hemorrhages)

  • Mucosal bleeding (epistaxis, gum bleeding, menorrhagia)

• Coagulation Factor Deficiencies (e.g., Hemophilia): Cause defects in secondary hemostasis (the stabilization of the plug with fibrin). This leads to bleeding from larger vessels, manifesting as:

  • a) Delayed deep tissue bleeding

  • c) Hemarthrosis (joint bleeding)

  • d) Retroperitoneal hematoma

• ADAMTS13 is a plasma enzyme that cleaves ultra-large von Willebrand factor (vWF) multimers into smaller, less adhesive forms.

• A severe deficiency of ADAMTS13 (typically <10% of normal activity), often due to an autoantibody, is the specific pathophysiology of Thrombotic Thrombocytopenic Purpura (TTP).

• This deficiency leads to the accumulation of ultra-large vWF multimers, which cause excessive platelet adhesion and aggregation in the microvasculature, leading to the characteristic thrombocytopenia and microangiopathic hemolytic anemia.

The other options are incorrect:

• b) Disseminated Intravascular Coagulation (DIC): Thrombocytopenia in DIC is due to consumption of platelets in widespread thrombi, not ADAMTS13 deficiency.

• c) Hemolytic Uremic Syndrome (HUS): Typical (diarrhea-associated) HUS is caused by Shiga toxin-producing bacteria, not ADAMTS13 deficiency. Atypical HUS involves dysregulation of the complement system.

• d) Idiopathic Thrombocytopenic Purpura (ITP): Thrombocytopenia in ITP is caused by autoimmune antibody-mediated platelet destruction.

• Abciximab is a monoclonal antibody that binds to and blocks the GPIIb/IIIa receptor on the platelet surface.

• This prevents the receptor from binding to fibrinogen, which is the final common pathway for platelet aggregation. It is a potent intravenous antiplatelet agent used in acute coronary syndromes.

The other mechanisms correspond to different antiplatelet drugs:

• a) ADP receptor antagonism: The mechanism of clopidogrel, ticagrelor, and prasugrel.

• c) Cyclooxygenase inhibition: The mechanism of aspirin.

• d) Phosphodiesterase inhibition: The mechanism of dipyridamole and cilostazol.

• In ITP, the low platelet count is due to peripheral destruction (by autoantibodies), not a problem with production.

• The bone marrow compensates for this destruction by increasing the production of megakaryocytes, which often appear normal or increased in number on a bone marrow biopsy.

The other options are incorrect:

• b) Decreased platelet production: This is the mechanism in aplastic anemia or marrow infiltration, not in ITP.

• c) Splenic atrophy: The spleen is often normal or enlarged in ITP as it is a site of platelet destruction; atrophy is not a feature.

• d) Prolonged PT and aPTT: These coagulation tests are normal in ITP, as it is a disorder of platelets, not coagulation factors.

• Storage pool disease specifically refers to deficiencies in the contents of platelet granules.

• A dense granule deficiency (δ-storage pool disease) is the most common type. Dense granules contain non-protein substances like ADP, ATP, calcium, and serotonin, which are crucial for amplifying the platelet activation response.

• There is also a less common alpha granule deficiency (α-storage pool disease), known as Gray Platelet Syndrome.

The other organelles are not the primary focus of this disorder:

• b) Mitochondria: Responsible for energy production, not specific granule storage.

• c) Lysosomes: Contain hydrolytic enzymes.

• d) Glycogen granules: Serve as an energy reserve

• Glanzmann thrombasthenia is a qualitative platelet disorder. Patients have a normal number of platelets, but a genetic defect in the GPIIb/IIIa receptor prevents them from aggregating properly, leading to severely impaired function and a bleeding tendency.

The other options are characterized by abnormal platelet counts:

• a) Idiopathic Thrombocytopenic Purpura (ITP): An autoimmune disorder causing low platelet count (thrombocytopenia).

• b) Thrombotic Thrombocytopenic Purpura (TTP): A thrombotic microangiopathy causing low platelet count (thrombocytopenia).

• d) May-Hegglin anomaly: A disorder characterized by giant platelets and thrombocytopenia (low platelet count).

• Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by:

  • Increased red blood cell mass

  • Often elevated platelets (thrombocytosis)

  • Sometimes elevated WBCs

• Mechanism: clonal proliferation of hematopoietic stem cells, affecting multiple lineages (RBCs, platelets, granulocytes).

• Clinical relevance:

  • Thrombocytosis in PV contributes to thrombotic risk, along with hyperviscosity from increased RBCs.

• May-Hegglin Anomaly is characterized by the presence of Döhle-like bodies. These are large, blue or blue-gray cytoplasmic inclusions in neutrophils (and sometimes other granulocytes) composed of aggregates of ribosomes and rough endoplasmic reticulum.

The other options are incorrect:

• a) Wiskott-Aldrich syndrome: Associated with small platelets and immunodeficiency, not specific blue inclusions in white cells.

• c) Ehlers-Danlos syndrome: A connective tissue disorder, not a hematologic condition with cellular inclusions.

• d) Hermansky-Pudlak syndrome: A disorder of platelet dense granules and oculocutaneous albinism, not blue inclusions in white cells.

• Reactive (secondary) thrombocytosis is far more common than primary thrombocythemia. The most frequent causes are acute and chronic inflammation or infection. In these conditions, cytokines like interleukin-6 (IL-6) stimulate thrombopoietin production, leading to increased platelet production.

The other options are incorrect:

• b) G6PD deficiency: This is a red blood cell enzyme disorder causing hemolytic anemia, not thrombocytosis.

• c) Vitamin B12 deficiency: This causes megaloblastic anemia and can sometimes cause mild thrombocytopenia, not thrombocytosis.

• d) Sickle cell disease: This is associated with functional asplenia, which can lead to mild, chronic thrombocytosis, but infection and inflammation are still the most common overall causes of a high platelet count.

• Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by:

  • Marked thrombocytosis (platelet counts often >600 × 10³/µL, here 900 × 10³/µL)

  • Giant, bizarre-shaped platelets on peripheral smear

  • Mild splenomegaly

  • Possible microvascular complications, e.g., painful extremities or joints

• Why not the other options:

  • Congenital spherocytosis → hemolytic anemia, spherocytes on smear, splenomegaly; platelets usually normal.

  • Rheumatoid arthritis with reactive thrombocytosis → platelet count usually moderately elevated; platelets normal in size/shape.

  • Myelofibrosis → presents with teardrop RBCs, leukoerythroblastic smear, variable platelet counts (often decreased), and significant marrow fibrosis.

• The GPIb/IX/V complex is the primary receptor on platelets for von Willebrand factor (vWF).

• This binding is crucial for the initial tethering and adhesion of platelets to the exposed subendothelium at sites of vascular injury, especially under high shear stress conditions (like in arteries).

The other receptors have different functions:

• a) GPIIb/IIIa: This is the receptor for fibrinogen, which mediates platelet aggregation (the clumping together of platelets), not the initial adhesion.

• c) GPIa/IIa: This is a receptor for collagen, involved in platelet adhesion and activation.

• d) GPIV: This is also a receptor for collagen and thrombospondin.

It’s crucial to distinguish between acute and chronic ITP:

• Acute ITP is primarily a childhood disease, often following a viral infection. Its hallmark is a sudden onset and spontaneous remission within weeks to months in the majority (80-90%) of cases.

The other options are characteristic of chronic ITP:

• a) It is found primarily in adults: Chronic ITP is more common in adults. Acute ITP is primarily a disease of children.

• c) Women are more commonly affected: This is true for chronic ITP, which has a female predominance. Acute ITP has an equal sex distribution.

• d) Peripheral destruction of platelets is decreased: This is incorrect for all forms of ITP. The core problem in ITP is increased peripheral destruction of platelets by autoantibodies.

• The bleeding time test measures the time it takes for a small, standardized skin incision to stop bleeding. This process, called primary hemostasis, relies heavily on platelet plug formation (platelet adhesion, activation, and aggregation) and vascular constriction.

• Therefore, a prolonged bleeding time typically indicates a problem with platelet function or number, or with blood vessel integrity.

The other options are incorrect:

• a) Coagulation factor deficiencies: These are assessed by tests like PT and aPTT, which measure the coagulation cascade (secondary hemostasis).

• c) Fibrinolysis: This is assessed by tests like D-dimer and fibrin degradation products (FDPs).

• d) Clot stability: This is not primarily evaluated by the bleeding time test.

• Hermansky-Pudlak syndrome is a rare autosomal recessive disorder characterized by the triad of:

  1. Oculocutaneous albinism (due to defective melanosome formation)

  2. Platelet storage pool deficiency (absence of dense granules), leading to a bleeding tendency and often mild thrombocytopenia

  3. Ceroid lipofuscin accumulation in lysosomes (which can cause pulmonary fibrosis and granulomatous colitis)

The other options are incorrect:

• a) Wiskott-Aldrich syndrome: Associated with thrombocytopenia, eczema, and immunodeficiency, but not albinism.

• b) May-Hegglin Anomaly: Associated with giant platelets, Döhle bodies, and thrombocytopenia, but not albinism.

• d) Chédiak-Higashi syndrome: Associated with albinism, but the platelet count is usually normal. Its hallmark is giant granules in leukocytes and recurrent infections.

• Platelet-type bleeding (disorders of primary hemostasis) typically involves bleeding from small vessels. This manifests as:

  • Petechiae: Pinpoint hemorrhages in the skin.

  • Mucosal bleeding: Such as epistaxis (nosebleeds), gum bleeding, and menorrhagia (heavy menstrual bleeding).

The other options are characteristic of coagulation factor-type bleeding (disorders of secondary hemostasis):

• a) Hemarthrosis (bleeding into joints)

• b) Deep muscle hematomas

• d) Delayed bleeding after trauma

• The ristocetin assay is a specific test used to evaluate the GPIb receptor on platelets and the function of von Willebrand factor (vWF).

• Ristocetin induces platelet agglutination by facilitating the binding of vWF to the GPIb receptor. This interaction is crucial for the initial adhesion of platelets to damaged vessel walls.

The other options are incorrect:

• a) GPIIb/IIIa: This is the fibrinogen receptor essential for the final common pathway of platelet aggregation (e.g., in response to ADP, collagen, epinephrine), not for ristocetin-induced agglutination.

• c) ADP receptor: This is involved in platelet activation and aggregation in response to ADP.

• d) Collagen: Binds to platelet receptors like GPVI to activate platelets, but is not the mechanism for ristocetin.

• Heparin-Induced Thrombocytopenia (HIT) is a prothrombotic disorder. It is characterized by a fall in platelet count (thrombocytopenia) that is paradoxically associated with a high risk of arterial and venous thrombosis. This is because the IgG antibodies formed against the heparin-PF4 complex activate platelets and promote a hypercoagulable state.

The other options are not characteristic of HIT:

• a) Increased platelet count: HIT causes thrombocytopenia, not thrombocytosis.

• c) Prolonged bleeding time only: HIT is a thrombotic, not a bleeding, disorder. Bleeding is uncommon.

• d) Increased fibrinogen: Fibrinogen levels are typically normal in HIT.

• Tirofiban is a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor. It directly blocks the final common pathway of platelet aggregation by preventing fibrinogen from binding to the activated GPIIb/IIIa receptor on platelets. This makes it a direct antiplatelet agent.

The other options are direct thrombin inhibitors (DTIs), which target the coagulation cascade, not platelets:

• a) Argatroban: A direct thrombin inhibitor.

• b) Hirudin: A direct thrombin inhibitor (originally from leech saliva).

• d) Dabigatran: An oral direct thrombin inhibitor.

• Wiskott-Aldrich syndrome is a rare X-linked recessive disorder characterized by the classic triad of:

  1. Eczema

  2. Recurrent infections (due to T- and B-cell dysfunction and impaired antibody production)

  3. Thrombocytopenia with small platelets

The other options are incorrect:

• a) Bernard–Soulier syndrome: Presents with thrombocytopenia, giant platelets, and bleeding, but not eczema or recurrent infections.

• b) Glanzmann thrombasthenia: Presents with a normal platelet count and normal platelet size, but defective platelet aggregation and bleeding. No immune dysfunction or eczema.

• d) Essential thrombocythemia: Presents with a high platelet count and thrombotic/hemorrhagic complications, not thrombocytopenia, eczema, or infections.

The key to this question is the combination of isolated thrombocytopenia (very low platelet count) with normal coagulation studies (PT and aPTT).

• c) ITP is an autoimmune disorder characterized by antibody-mediated platelet destruction. It specifically causes a low platelet count without affecting the coagulation cascade, so the PT and aPTT remain normal.

The other options would typically cause abnormalities in coagulation studies:

• a) DIC: Causes consumption of both platelets and coagulation factors, leading to thrombocytopenia and prolonged PT/aPTT.

• b) Vitamin K deficiency: Impairs the synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X), leading to a prolonged PT (and often aPTT), not an isolated low platelet count.

• d) Liver disease: The liver produces most coagulation factors. Liver disease causes a coagulopathy with prolonged PT/aPTT. Thrombocytopenia can also occur due to portal hypertension and splenic sequestration, but the coagulation studies would not be normal.

• Thrombotic Thrombocytopenic Purpura (TTP) is primarily caused by a severe deficiency (typically autoantibody-mediated) of the enzyme ADAMTS13 (A Disintegrin And Metalloproteinase with a Thrombospondin type 1 motif, member 13).

• This enzyme is responsible for cleaving ultra-large von Willebrand factor (vWF) multimers into smaller, less adhesive forms. In its absence, these ultra-large multimers persist in the blood, causing excessive platelet adhesion and aggregation, leading to the widespread microthrombi that define the disease.

The other options are incorrect:

• a) Factor VIII: A deficiency causes Hemophilia A.

• c) Fibrinogen: A deficiency causes afibrinogenemia, a bleeding disorder.

• d) Thrombin: A deficiency would cause a severe bleeding disorder, not TTP.

• Aspirin-induced platelet dysfunction is a common acquired condition resulting from medication use. Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), impairing thromboxane A2 production and platelet aggregation.

The other options are all inherited disorders:

• a) Glanzmann thrombasthenia: Autosomal recessive disorder of the GPIIb/IIIa receptor.

• b) Bernard–Soulier syndrome: Autosomal recessive disorder of the GPIb-IX-V complex.

• d) Wiskott–Aldrich syndrome: X-linked recessive disorder.

• Scenario: Postoperative patient with normal PT/aPTT/fibrinogen but low platelet count (40 × 10³/µL) and wound oozing.

• This pattern suggests bleeding due to low platelet numbers, not a coagulation factor defect.

• Dilutional thrombocytopenia can occur after:

  • Massive transfusions with red cells or crystalloids that lack platelets.

  • Hemodilution → reduced platelet concentration, leading to bleeding despite normal coagulation tests.

• Dilution of coagulation factors → would prolong PT/aPTT.

• Intravascular coagulation (DIC) → would show prolonged PT/aPTT, low fibrinogen, elevated D-dimers.

• Hypofibrinogenemia → low fibrinogen and prolonged PT/aPTT.

• Thrombocytopenia is the medical term for a low platelet count, defined as less than 150,000 platelets per microliter (150 × 10⁹/L).

The other options describe different conditions:

• b) Thrombocytosis: An elevated platelet count (above 450 × 10⁹/L).

• c) Pancytopenia: A reduction in all three major blood cell lines (red blood cells, white blood cells, and platelets).

• d) Leukocytosis: An elevated white blood cell count.

• Heparin-Induced Thrombocytopenia (HIT) is caused by antibodies that recognize neoantigens formed when heparin binds to Platelet Factor 4 (PF4), a chemokine released from platelet alpha granules.

• These IgG antibodies bind to the PF4/heparin complex, and the Fc portion of the antibody then binds to FcγRIIa receptors on platelets and monocytes. This triggers massive platelet activation, consumption (leading to thrombocytopenia), and a high risk of thrombosis.

The other options are associated with different conditions:

• a) Anticardiolipin (ACLA) & d) Beta-2-glycoprotein 1 (B2GP1): These are the targets of antiphospholipid antibodies in Antiphospholipid Syndrome.

• c) Antithrombin (AT): Heparin’s normal mechanism of action is to potentiate antithrombin, but antibodies are not formed against antithrombin itself in HIT.

• Platelet disorders (defects in primary hemostasis) typically cause bleeding from small vessels, especially in mucous membranes and the skin. This includes:

  • Epistaxis (nosebleeds)

  • Gum bleeding

  • Menorrhagia (heavy menstrual bleeding)

  • Petechiae and easy bruising

The other options are characteristic of coagulation factor deficiencies (defects in secondary hemostasis):

• a) Hemarthrosis (joint bleeding)

• b) Delayed bleeding

• c) Deep hematomas

• Wiskott-Aldrich syndrome is a rare X-linked recessive disorder classically presenting with the triad of:

  1. Thrombocytopenia (with small platelets)

  2. Eczema

  3. Immunodeficiency (defective T-cell function and impaired antibody responses, leading to recurrent infections)

The other options are incorrect:

• b) May-Hegglin Anomaly: Characterized by thrombocytopenia, giant platelets, and Döhle bodies, but no eczema or immunodeficiency.

• c) Hermansky-Pudlak syndrome: Characterized by oculocutaneous albinism and a platelet storage pool defect, but not classic eczema or the same type of immunodeficiency.

• d) Scott syndrome: A very rare disorder of platelet procogaulant activity (defect in membrane phospholipid scrambling), not associated with this triad.

This question distinguishes between quantitative (problems with platelet number) and qualitative (problems with platelet function) disorders.

• d) May-Hegglin anomaly: This is a quantitative disorder. It is characterized by thrombocytopenia (a low platelet count), along with giant platelets and Döhle-like inclusions in white cells.

The other options are qualitative platelet or coagulation disorders:

• a) Von Willebrand disease: A qualitative disorder affecting von Willebrand factor, which is crucial for platelet adhesion. Platelet count is normal.

• b) Hemophilia A: A coagulation factor (VIII) deficiency, not a platelet disorder. Platelet count and function are normal.

• c) Glanzmann thrombasthenia: A qualitative platelet disorder where platelet count is normal, but function is impaired due to a GPIIb/IIIa receptor defect.

• Immune thrombocytopenia (ITP) is a classic and common cause of thrombocytopenia, where the immune system produces antibodies that target and destroy platelets.

The other options are incorrect:

• a) Iron deficiency anemia: This primarily causes microcytic anemia. Platelet counts can be variable, but thrombocytopenia is not a defining feature.

• c) Vitamin B12 deficiency: This causes megaloblastic anemia and can sometimes cause mild thrombocytopenia, but it is not a common primary cause of isolated, significant thrombocytopenia.

• d) Erythropoietin deficiency: This leads to anemia (e.g., in chronic kidney disease), not thrombocytopenia.

While thrombocytosis is the general term for a high platelet count, a sustained, significant elevation above 600 × 10⁹/L in the absence of a reactive cause is highly suggestive of a myeloproliferative neoplasm, most commonly Essential Thrombocythemia (ET).

• a) Reactive thrombocytosis: This is a secondary, non-clonal increase in platelets, usually due to conditions like inflammation, infection, or iron deficiency. The count is often elevated but typically not as persistently or extremely high as in ET.

• c) Polycythemia: This refers to an increase in red blood cell mass, not platelets.

• d) Pancytopenia: This is a decrease in all cell lines, the opposite of what is described.

• Platelet disorders (problems with primary hemostasis) typically manifest as bleeding from small vessels. This includes:

  • Petechiae: Pinpoint hemorrhages in the skin.

  • Mucosal bleeding: Such as epistaxis (nosebleeds), gum bleeding, and menorrhagia (heavy menstrual bleeding).

The other options are more characteristic of coagulation factor disorders (problems with secondary hemostasis):

• a) Deep muscle bleeding

• b) Joint bleeding (hemarthrosis)

• d) Retroperitoneal hemorrhage

• Increased fibrinogen is an acute phase reactant that can be elevated in inflammation, infection, or pregnancy. It is not a mechanism that causes a low platelet count.

The other options are well-established causes of thrombocytopenia:

• a) Splenic sequestration: Platelets can be trapped and destroyed in an enlarged spleen (hypersplenism).

• b) Decreased marrow production: This occurs in conditions like aplastic anemia, leukemia, myelodysplastic syndromes, and chemotherapy.

• c) Increased destruction: This is the mechanism in Immune Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP), and Disseminated Intravascular Coagulation (DIC).

• Aplastic anemia is defined by pancytopenia resulting from bone marrow hypocellularity and a failure of hematopoiesis. This failure affects all three cell lines:

  • Red blood cells (leading to anemia)

  • White blood cells (leading to leukopenia/neutropenia)

  • Platelets (leading to thrombocytopenia)

• Gray platelet syndrome is a rare inherited platelet disorder characterized by a deficiency or abnormality of alpha granules.

• These granules contain proteins like fibrinogen, von Willebrand factor, platelet factor 4, and thrombospondin. Their absence makes the platelets appear pale or gray on a peripheral blood smear, giving the syndrome its name.

The other options are incorrect:

• a) Dense granules: A deficiency of dense granules (which contain ADP, ATP, calcium, and serotonin) is seen in δ-storage pool disease.

• c) Lysosomal enzymes: This is not a specific feature of gray platelet syndrome.

• d) GPIb receptor: A deficiency of the GPIb receptor causes Bernard-Soulier syndrome.

• Immune Thrombocytopenic Purpura (ITP) is an autoimmune disorder where the immune system produces antibodies that target and destroy platelets, leading to isolated thrombocytopenia.

The other options are incorrect:

• a) Hemophilia: This is caused by a genetic deficiency of clotting factors (VIII or IX), not autoimmune platelet destruction.

• c) TTP: This is a thrombotic microangiopathy primarily caused by a deficiency of the ADAMTS13 enzyme, leading to platelet aggregation, not primarily autoimmune destruction.

• d) Polycythemia vera: This is a myeloproliferative neoplasm characterized by the overproduction of red blood cells, not autoimmune platelet destruction.

This range (150,000 to 450,000 platelets per microliter of blood) is the widely accepted standard for a normal platelet count in adults.

• Values below 150 × 10⁹/L indicate thrombocytopenia.

• Values above 450 × 10⁹/L indicate thrombocytosis.

The bleeding time test primarily assesses primary hemostasis, which depends on platelet function and vascular integrity.

• c) Severe von Willebrand disease: Von Willebrand factor (vWF) is crucial for platelet adhesion to the subendothelium. A severe deficiency profoundly disrupts the formation of the initial platelet plug, leading to a markedly prolonged bleeding time.

The other options are disorders of secondary hemostasis (the coagulation cascade), which do not significantly affect the bleeding time:

• a) Hemophilia A (Factor VIII deficiency)

• b) Vitamin K deficiency (affects Factors II, VII, IX, X)

• d) Mild factor XI deficiency

• Glanzmann thrombasthenia is a rare autosomal recessive disorder caused by a deficiency or dysfunction of the GPIIb/IIIa complex (also known as integrin αIIbβ3).

• This receptor is essential for platelet aggregation, as it is the primary receptor for fibrinogen, which cross-links platelets to form a clot.

The other options are associated with different disorders:

• a) GPIb receptor: A defect here causes Bernard-Soulier syndrome, which impairs platelet adhesion.

• c) ADAMTS13 deficiency: This causes thrombotic thrombocytopenic purpura (TTP).

• d) Collagen binding: Impaired collagen binding can be a feature of various platelet function defects but is not the specific cause of Glanzmann thrombasthenia.

• Ticlopidine and clopidogrel are P2Y12 ADP receptor antagonists. They irreversibly block the P2Y12 subtype of the ADP receptor on the platelet surface.

• This inhibition prevents ADP from amplifying the platelet activation response and the conformational change in the GPIIb/IIIa receptor necessary for stable platelet aggregation.

The other options describe different mechanisms:

• a) Binding von Willebrand factor: This is the mechanism of some novel therapies, but not ticlopidine/clopidogrel.

• c) Blocking the GPIIb/IIIa receptor: This is the mechanism of drugs like abciximab, eptifibatide, and tirofiban.

• d) Depleting platelet alpha granule content: This is not a known mechanism of any common antiplatelet drug.

• Platelet satellitism is a rare, artifactual phenomenon observed on peripheral blood smears made from blood collected in the anticoagulant EDTA.

• In this artifact, platelets adhere to and surround neutrophils (or sometimes other leukocytes), forming rosettes. This is an in-vitro effect caused by EDTA-induced exposure of cryptic antigens and the action of autoantibodies. It has no clinical significance but can lead to a falsely low automated platelet count (pseudothrombocytopenia).

The other options are not associated with this specific phenomenon:

• b) Heparin therapy: Does not cause platelet satellitism.

• c) Vitamin K deficiency: Causes a coagulation factor deficiency, not a platelet artifact.

• d) Thrombocytopenia: This is a low platelet count, which can be a real condition or, in this context, a false result caused by the satellitism.

• The bleeding tendency in uremia is mainly caused by a qualitative platelet dysfunction, not a decrease in platelet count.

• Uremic toxins (e.g., guanidinosuccinic acid, phenol) interfere with platelet adhesion and aggregation. They impair the interaction between von Willebrand factor and platelet GPIb, reduce platelet dense granule release, and alter prostaglandin metabolism.

The other options are not the primary cause in uremia:

• a) Thrombocytopenia: The platelet count is usually normal in uremia.

• c) Factor VIII deficiency: Factor VIII levels are normal in uremia.

• d) Hyperfibrinolysis: This is not a typical feature of uremia.

• Bernard-Soulier syndrome is a rare inherited bleeding disorder caused by a quantitative or qualitative defect in the GPIb/IX/V complex.

• This receptor is essential for the initial adhesion of platelets to the site of vascular injury, as it is the primary receptor for von Willebrand factor (vWF). The defect leads to impaired platelet adhesion, giant platelets, and thrombocytopenia.

The other receptors are associated with different disorders or functions:

• b) GPIIb/IIIa: A defect here causes Glanzmann thrombasthenia.

• c) GPIa/IIa: This is a collagen receptor.

• d) GPIV: This is a receptor for collagen and thrombospondin.

• Bernard-Soulier syndrome is characterized by the triad of:

  1. Giant platelets (on peripheral smear)

  2. Defective platelet adhesion due to a deficiency of the GPIb-IX-V receptor complex (which binds von Willebrand factor)

  3. Thrombocytopenia

The other options are incorrect:

• a) Glanzmann thrombasthenia: Characterized by defective platelet aggregation due to a GPIIb/IIIa deficiency. Platelet size is normal.

• c) Wiskott-Aldrich syndrome: Characterized by small platelets, thrombocytopenia, eczema, and immunodeficiency.

• d) Gray platelet syndrome: Characterized by platelets that appear gray due to the absence of alpha-granules. Platelet adhesion may be affected, but giant platelets are not the hallmark.

• Bernard-Soulier syndrome is a rare inherited platelet disorder caused by a defect or deficiency in the GPIb-IX-V complex on the platelet surface.

• This receptor is essential for platelet adhesion, as it is the primary receptor for von Willebrand factor (vWF), allowing platelets to bind to damaged subendothelium.

The other options are associated with different disorders:

• b) GPIIb/IIIa receptor: A deficiency in this fibrinogen receptor causes Glanzmann thrombasthenia, which impairs platelet aggregation.

• c) Factor VIII: A deficiency causes Hemophilia A.

• d) vWF: A deficiency causes von Willebrand disease.

• Glanzmann thrombasthenia is a rare autosomal recessive disorder caused by a deficiency or dysfunction of the GPIIb/IIIa complex (also known as integrin αIIbβ3).

• This receptor is essential for platelet aggregation, as it is the primary receptor for fibrinogen, which cross-links platelets to form a clot. Without functional GPIIb/IIIa, platelets cannot aggregate properly, leading to a severe bleeding tendency.

The other receptors have different functions:

• a) GPIb/IX/V: A defect in this complex causes Bernard-Soulier syndrome, which impairs platelet adhesion.

• c) GPIa/IIa: This is a receptor for collagen.

• d) GPIV: This is a receptor for collagen and thrombospondin

• MPV is the platelet equivalent of the red cell MCV. It measures the average size of platelets in a blood sample.

• A high MPV indicates larger, younger platelets (often seen in increased platelet turnover like ITP).

• A low MPV indicates smaller, older platelets (seen in conditions like Wiskott-Aldrich syndrome).

The other options measure different things:

• b) MCV (Mean Corpuscular Volume): Measures the average size of red blood cells.

• c) PDW (Platelet Distribution Width): Measures the variation in platelet size (anisocytosis).

• d) RDW (Red cell Distribution Width): Measures the variation in red blood cell size.

• Thrombocytopenia is a disorder of primary hemostasis (the initial platelet plug). It typically causes bleeding from small vessels.

• This manifests as mucocutaneous bleeding, such as:

  • Petechiae (pinpoint hemorrhages in the skin)

  • Epistaxis (nosebleeds)

  • Gum bleeding

  • Menorrhagia (heavy menstrual bleeding)

The other options are more characteristic of coagulation factor deficiencies (disorders of secondary hemostasis):

• a) Hemarthrosis (joint bleeding)

• c) Deep muscle hematomas

• d) Intracranial hemorrhage (While this can occur in severe thrombocytopenia, it is a less common and more catastrophic event compared to widespread petechiae and epistaxis.)

• Platelets (thrombocytes) are small, anucleate cell fragments derived from megakaryocytes in the bone marrow.

• Their normal lifespan in peripheral blood is approximately 7–10 days.

• Senescent or damaged platelets are removed mainly by the spleen and liver.

• Clinical relevance:

  • Drugs like aspirin irreversibly inhibit platelet function for the entire platelet lifespan (~10 days).

  • In disorders with accelerated destruction (e.g., ITP), platelet count drops faster than production, leading to thrombocytopenia.

The classic pentad for TTP (often recalled by the mnemonic FAT RN) includes:

• Fever

• Anemia (microangiopathic hemolytic)

• Thrombocytopenia

• Renal dysfunction

• Neurological symptoms

The patient’s presentation with the key triad of thrombocytopenia, neurological symptoms, and microangiopathic hemolytic anemia (MAHA) is highly characteristic of TTP.

Let’s review the other options:

• a) ITP: Presents with isolated thrombocytopenia and bleeding. It does not cause MAHA or neurological symptoms.

• b) HUS: Typically presents with the triad of MAHA, thrombocytopenia, and renal failure. Severe neurological symptoms are more characteristic of TTP.

• d) HIT: Causes thrombocytopenia and thrombosis, but not microangiopathic hemolytic anemia.

• ITP is characterized by isolated thrombocytopenia due to immune-mediated platelet destruction.

• The PT (Prothrombin Time) and aPTT (Activated Partial Thromboplastin Time) are normal because ITP is a disorder of primary hemostasis (platelets) and does not involve the coagulation cascade (secondary hemostasis).

The other options are incorrect:

• b) Prolonged PT, prolonged aPTT: This indicates a coagulation factor deficiency (e.g., hemophilia, liver disease), not ITP.

• c) Pancytopenia: This indicates a problem with bone marrow production (e.g., aplastic anemia, MDS), not the peripheral destruction seen in ITP.

• d) Increased fibrin degradation products: This is seen in conditions like Disseminated Intravascular Coagulation (DIC), not ITP.

• Platelet aggregation studies directly assess how well platelets clump together in response to various agonists (like ADP, epinephrine, collagen, and ristocetin). This is the primary functional test for diagnosing conditions like von Willebrand disease, Glanzmann thrombasthenia, and aspirin/clopidogrel effects.

The other options are incorrect:

• a) PT (Prothrombin Time): Evaluates the extrinsic and common pathways of the coagulation cascade (factors VII, X, V, II, and fibrinogen).

• b) aPTT (Activated Partial Thromboplastin Time): Evaluates the intrinsic and common pathways of the coagulation cascade (factors XII, XI, IX, VIII, X, V, II, and fibrinogen).

• d) Serum ferritin: Measures iron stores and is used to diagnose iron deficiency, not platelet function.

• Aspirin irreversibly acetylates cyclooxygenase-1 (COX-1) in platelets.

• This inhibition blocks the conversion of arachidonic acid to prostaglandin G2 and H2, thereby preventing the synthesis of thromboxane A2 (TXA2), a potent promoter of platelet aggregation and vasoconstriction.

The other options are incorrect:

• a) Thromboxane synthase: This is the enzyme that converts prostaglandin H2 to thromboxane A2. Aspirin acts upstream, on cyclooxygenase.

• b) Phospholipase A2: This enzyme releases arachidonic acid from membrane phospholipids. Aspirin does not inhibit this enzyme.

• d) ADP receptor: This is a separate pathway for platelet activation; aspirin does not block the ADP receptor.

• Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1), reducing thromboxane A2 production and impairing platelet aggregation. This defect in primary hemostasis is detected by a prolonged bleeding time.

The other options are not affected by aspirin:

• a) PT (Prothrombin Time): Measures the extrinsic and common coagulation pathways; unaffected by aspirin.

• b) aPTT (Activated Partial Thromboplastin Time): Measures the intrinsic and common coagulation pathways; unaffected by aspirin.

• d) Serum ferritin: Measures iron stores; unaffected by aspirin.

The classic pentad for TTP (often recalled by the mnemonic FAT RN) includes:

• Fever

• Anemia (microangiopathic hemolytic)

• Thrombocytopenia

• Renal failure

• Neurological abnormalities

While the full pentad is not always present, the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure is highly characteristic of TTP (or its close relative, HUS). TTP is specifically caused by a severe deficiency of ADAMTS13, leading to uncontrolled platelet aggregation.

Let’s review the other options:

• a) Hemophilia A: This is a coagulation factor deficiency (Factor VIII) causing a bleeding disorder, not a thrombotic microangiopathy.

• b) Disseminated intravascular coagulation (DIC): DIC can cause MAHA and thrombocytopenia, but its primary driver is uncontrolled activation of the coagulation cascade, leading to consumption of clotting factors and a resulting bleeding diathesis. Renal failure can occur, but the coagulation profile (prolonged PT/aPTT, low fibrinogen, elevated D-dimer) is very different from TTP.

• d) Von Willebrand disease: This is the most common inherited bleeding disorder, characterized by deficient or defective von Willebrand factor. It does not cause thrombosis, MAHA, or renal failure.