Free ASCP MLS Exam Practice Questions Mock Test: Part 41 – Hemostasis & Coagulation Disorders

• Thrombin time specifically measures the final step of coagulation, which is the conversion of fibrinogen to fibrin by thrombin.

• Prolonged TT can occur due to:

  • Low fibrinogen (hypofibrinogenemia)

  • Abnormal fibrinogen (dysfibrinogenemia)

  • Presence of thrombin inhibitors (e.g., heparin, direct thrombin inhibitors)

Other options:

• a) PT → measures extrinsic and common pathways

• b) aPTT → measures intrinsic and common pathways

• d) D-dimer → indicates fibrinolysis (breakdown of cross-linked fibrin), not fibrin formation

• Bernard-Soulier syndrome is a rare inherited bleeding disorder caused by a defect in the GPIb/IX/V complex, which is the primary receptor for von Willebrand factor (vWF).

• This defect prevents platelets from adhering to damaged blood vessel walls, which is the first step in primary hemostasis.

Why the other options are incorrect:

• a) Defective GPIIb/IIIa receptor: This is the characteristic finding in Glanzmann thrombasthenia.

• c) Deficiency of ADP receptors: This is not a classic finding in a major defined platelet disorder. ADP receptor defects (e.g., P2Y12 deficiency) are rare and cause impaired aggregation.

• d) Lack of dense granules: This is a characteristic of δ-storage pool deficiency (a type of storage pool disease).

• ADAMTS13 is a protease that cleaves ultra-large von Willebrand factor (vWF) multimers.

• In TTP, ADAMTS13 deficiency (congenital or acquired) leads to accumulation of ultra-large vWF multimers, which cause platelet aggregation in small vessels, resulting in:

  • Thrombocytopenia

  • Microangiopathic hemolytic anemia

  • Potential organ damage (kidneys, CNS)

Other options:

• b) DIC → caused by widespread activation of coagulation, not ADAMTS13 deficiency.

• c) HUS → usually triggered by Shiga toxin; ADAMTS13 is typically normal.

• d) ITP → autoimmune platelet destruction, unrelated to ADAMTS13.

Von Willebrand factor (VWF) is a crucial protein for primary hemostasis. It acts as a bridge between exposed collagen at a site of vascular injury and platelets.

• The specific receptor on the platelet surface for VWF is the glycoprotein Ib/IX/V complex (GPIb/IX/V).

• This initial binding, especially under high shear stress (like in arterioles), is the primary mechanism for platelet adhesion.

Why the other options are incorrect:

• a) GPIIb/IIIa: This is the receptor for fibrinogen (and VWF), and it is the final common pathway for platelet aggregation, not the initial adhesion.

• c) GPIa/IIa: This is an integrin receptor for collagen, mediating direct platelet adhesion to collagen.

• d) GPIV: This is also known as CD36 and is a receptor for thrombospondin and collagen, but it plays a less critical role compared to GPIb/IX/V for VWF-mediated adhesion.

• Factor VII is part of the extrinsic pathway of coagulation.

• Deficiency of factor VII leads to:

  • Prolonged PT (extrinsic pathway affected)

  • Normal aPTT (intrinsic pathway unaffected)

• Causes include: congenital factor VII deficiency, vitamin K deficiency, or warfarin therapy.

Other options:

• b) Factor VIII → intrinsic pathway → prolonged aPTT, normal PT (Hemophilia A)

• c) Factor IX → intrinsic pathway → prolonged aPTT, normal PT (Hemophilia B)

• d) Factor XI → intrinsic pathway → prolonged aPTT, normal PT (Hemophilia C)

• Mixing studies involve mixing the patient’s plasma with normal plasma in a 1:1 ratio and repeating the coagulation test (usually aPTT or PT).

• Interpretation:

  • Correction of the prolonged clotting time → suggests a factor deficiency (normal plasma supplies the missing factor).

  • No correction → suggests the presence of an inhibitor (e.g., lupus anticoagulant, specific factor inhibitor) that interferes with coagulation even in the presence of normal plasma.

Other options:

• a) Platelet vs coagulation factor disorders → diagnosed by platelet count, bleeding time, and aggregation studies

• c) Extrinsic vs intrinsic pathway → determined by PT vs aPTT

• d) Primary vs secondary hemostasis → bleeding time vs PT/aPTT

Platelet-related bleeding disorders (such as immune thrombocytopenia, Glanzmann thrombasthenia, or Bernard-Soulier syndrome) typically cause a pattern of bleeding from mucocutaneous (skin and mucous membrane) sites.

Why the other options are incorrect:

• a) Hemarthrosis: This is bleeding into joints and is the hallmark of coagulation factor deficiencies like hemophilia A and B. It is very uncommon in pure platelet disorders.

• b) Delayed bleeding: This is characteristic of coagulation disorders (like hemophilia or factor deficiencies), where the initial platelet plug forms but is not stabilized by a stable fibrin clot. Bleeding in platelet disorders is typically immediate.

• c) Deep hematomas: Large, palpable muscle and soft tissue hematomas are more typical of severe coagulation factor deficiencies, not platelet disorders.

• Protein C is a vitamin K–dependent natural anticoagulant.

• Activated protein C (APC) inactivates:

  • Factor Va

  • Factor VIIIa

• This helps regulate clot formation and prevents excessive thrombosis.

• Protein C deficiency → increased risk of venous thromboembolism and, in severe cases, purpura fulminans.

Other options:

• a) Factor VIII → procoagulant factor; deficiency causes Hemophilia A

• c) Factor IX → procoagulant factor; deficiency causes Hemophilia B

• d) Fibrinogen (Factor I) → procoagulant; converted to fibrin

• aPTT (activated partial thromboplastin time) measures the intrinsic and common coagulation pathways.

• It evaluates deficiencies or inhibitors of factors XII, XI, IX, VIII, as well as common pathway factors (X, V, II, fibrinogen).

• Prolonged aPTT is seen in:

  • Hemophilia A (factor VIII deficiency)

  • Hemophilia B (factor IX deficiency)

  • Factor XI deficiency

  • Heparin therapy

Other options:

• a) Extrinsic → measured by PT

• c) Platelet → measured by bleeding time

• d) Fibrinolysis → measured by D-dimer

• Glanzmann thrombasthenia is a qualitative platelet disorder. It is caused by a deficiency or dysfunction of the glycoprotein IIb/IIIa complex on the platelet surface, which is necessary for platelet aggregation.

• Patients have a normal platelet count but suffer from abnormal platelet function, leading to a bleeding tendency.

Why the other options are incorrect:

• a) Idiopathic Thrombocytopenic Purpura (ITP): This is characterized by a low platelet count (thrombocytopenia). The function of the remaining platelets is generally normal.

• b) Thrombotic Thrombocytopenic Purpura (TTP): This is characterized by a severely low platelet count (thrombocytopenia) due to microthrombus formation.

• d) May-Hegglin anomaly: This is characterized by a low platelet count (thrombocytopenia) and the presence of giant platelets.

The bleeding time test is a measure of primary hemostasis, which involves platelet plug formation and blood vessel contraction.

• c) Severe von Willebrand disease: Von Willebrand factor (vWF) is critical for platelet adhesion to the subendothelium. A severe deficiency directly impairs the very first step of primary hemostasis, leading to a prolonged bleeding time.

Why the other options are incorrect:

• a) Factor VIII deficiency: This affects the coagulation cascade (secondary hemostasis). While it causes bleeding, it does not directly affect platelet plug formation, so the bleeding time is typically normal. This is the defect in Hemophilia A.

• b) Vitamin K deficiency: This leads to a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, X). Like Factor VIII deficiency, this impairs the coagulation cascade, not primary hemostasis. The bleeding time is usually normal.

• d) Mild factor XI deficiency: Factor XI is part of the coagulation cascade. A mild deficiency often has a variable bleeding tendency, but the bleeding time is generally not affected.

• Vitamin K–dependent coagulation factors require vitamin K for gamma-carboxylation of glutamic acid residues, which is necessary for calcium binding and proper function.

• The vitamin K–dependent factors are:

  • II (Prothrombin), VII, IX, X

  • Proteins C and S (anticoagulant proteins)

• Factor V, VIII, XI are not vitamin K–dependent.

• Lupus anticoagulant (LA) is an antiphospholipid antibody that interferes with phospholipid-dependent coagulation tests, especially aPTT, causing it to be prolonged in vitro.

• Paradoxically, patients with LA have an increased risk of thrombosis (arterial and venous), rather than bleeding.

• It is commonly associated with antiphospholipid syndrome (APS).

Other options:

• a) Prolonged PT and bleeding tendency → not typical for LA

• c) Normal coagulation tests → LA usually prolongs aPTT

• d) Isolated thrombocytopenia → may occur in some autoimmune conditions but is not diagnostic of LA

Warfarin works by inhibiting vitamin K–dependent synthesis of clotting factors II, VII, IX, and X.
The prothrombin time (PT) is particularly sensitive to deficiencies in factors II, VII, and X, so it becomes prolonged with warfarin therapy.

Other options:

• a) Bleeding time → measures platelet function, not affected by warfarin

• b) Thrombin time → measures conversion of fibrinogen to fibrin; not affected by warfarin

• d) Activated clotting time (ACT) → mainly used to monitor heparin therapy

• Hemophilia A is an X-linked recessive bleeding disorder caused by deficiency or dysfunction of factor VIII.

• Factor VIII is part of the intrinsic pathway, so patients typically present with:

  • Prolonged aPTT

  • Normal PT

  • Normal platelet count

• Clinical features include hemarthroses, deep muscle hematomas, and prolonged bleeding after trauma.

Other options:

• b) Factor IX → deficiency causes Hemophilia B (Christmas disease)

• c) Factor XI → deficiency causes Hemophilia C

• d) Factor XII → deficiency usually does not cause bleeding, mainly affects lab tests

The activated partial thromboplastin time (aPTT) test is primarily used to evaluate the intrinsic pathway (factors XII, XI, IX, VIII) and the common pathway (factors II, V, X, fibrinogen).
It is most sensitive to deficiencies in the intrinsic pathway.

Other options:

• b) Extrinsic pathway → measured by PT

• c) Common pathway → contributes to both PT and aPTT, but aPTT is most sensitive to intrinsic factors

• d) Fibrinolytic pathway → not evaluated by aPTT

• May-Hegglin anomaly is a rare, inherited disorder characterized by thrombocytopenia (a low platelet count). This makes it a quantitative platelet disorder. Additionally, it features large platelets and characteristic inclusions (Döhle-like bodies) in white blood cells.

Why the other options are incorrect (they are qualitative or coagulation disorders):

• a) Von Willebrand disease: This is primarily a disorder of platelet function (a qualitative defect) due to defective or deficient von Willebrand factor, which is needed for proper platelet adhesion. The platelet count is normal.

• b) Hemophilia A: This is a coagulation factor disorder (deficiency of Factor VIII), not a platelet disorder at all. Platelet count and function are normal.

• c) Glanzmann thrombasthenia: This is a qualitative platelet disorder. The platelet count is normal, but there is a functional defect due to a deficiency or abnormality of the GPIIb/IIIa receptor, which prevents platelets from aggregating.

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

1. Endothelial cells (primary site of synthesis)

2. Megakaryocytes

Since the question asks for the cell type and only one option is to be chosen, Endothelial cells (b) is the best and most fundamental answer.

Breakdown of the options:

• a) Hepatocytes: These are the primary site for synthesis of most coagulation factors (like II, VII, IX, X, fibrinogen), but not vWF.

• b) Endothelial cells: Correct. This is the major site of vWF synthesis and storage in Weibel-Palade bodies.

• c) Megakaryocytes: Also correct as a site of synthesis. vWF produced here is packaged into platelet alpha-granules. However, endothelial cells are considered the primary source.

• d) Monocytes: These are not involved in the synthesis of vWF.

• • Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency) affect the intrinsic coagulation pathway.

  • Activated partial thromboplastin time (aPTT) measures the intrinsic and common pathways, so it is prolonged in both disorders.

  • Other tests are usually normal:

    • PT → normal (extrinsic pathway unaffected)

    • Thrombin time (TT) → normal (fibrinogen to fibrin step intact)

    • Bleeding time → normal (platelet number and function are normal)

• Essential Thrombocythemia (ET) is a myeloproliferative disorder characterized by:

  • Marked thrombocytosis (platelet counts often >600–1,000 × 10³/µL)

  • Giant and bizarre-shaped platelets on peripheral smear

  • Sometimes abnormal platelet function, leading to bleeding or thrombosis

Other options:

• a) Reactive thrombocytosis → usually mild to moderate platelet elevation (<600 × 10³/µL) and platelets are morphologically normal.

• b) Myelofibrosis → often shows teardrop RBCs, variable platelet counts, not usually giant bizarre platelets.

• d) Congenital spherocytosis → red cell membrane defect; platelets are typically normal.

Uremia leads to dysfunctional platelets due to the accumulation of toxic metabolites that impair platelet adhesion and aggregation, rather than causing significant thrombocytopenia, factor deficiency, or hyperfibrinolysis.

Other options:

• a) ADP receptor antagonism → mechanism of clopidogrel, ticlopidine

• c) Cyclooxygenase inhibition → mechanism of aspirin

• d) Phosphodiesterase inhibition → mechanism of dipyridamole, cilostazol

• Factor V Leiden is a genetic mutation in factor V that makes it resistant to inactivation by activated protein C (APC).

• This leads to prolonged activity of factor V, causing excess thrombin generation and a hypercoagulable state.

• Clinically, patients have an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Other options:

• a) Hemophilia A → deficiency of factor VIII, bleeding disorder, not thrombosis

• c) vWD → platelet adhesion defect, bleeding disorder

• d) DIC → consumptive coagulopathy with bleeding and microthrombi; not specifically associated with factor V Leiden

D-dimer is a degradation product of cross-linked fibrin, indicating that fibrinolysis has occurred. It is commonly elevated in conditions like deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC).

Other options:

• b) Platelet count → measured directly, not related to D-dimer

• c) Fibrinogen activity → assessed by fibrinogen level or thrombin time, not D-dimer

• d) Factor XIII deficiency → affects fibrin stabilization, not measured by D-dimer

Acute Idiopathic Thrombocytopenic Purpura (ITP), now more commonly called Immune Thrombocytopenia, has two distinct forms: acute and chronic. The description in the question refers to the acute form, which is primarily a childhood disease.

• b) Spontaneous remission usually occurs within several weeks: This is the hallmark of acute ITP. It often follows a viral infection, and in about 80% of children, the condition resolves spontaneously within 6 months, often within a few weeks, even without treatment.

Why the other options are incorrect:

• a) It is found primarily in adults: This is false. The acute form is found primarily in children (ages 2-6 years). The chronic form is more common in adults.

• c) Women are more commonly affected: This is true for chronic ITP, which has a female predominance. The acute childhood form has an equal sex distribution or a slight male predominance.

• d) Peripheral destruction of platelets is decreased: This is the opposite of the truth. ITP is characterized by increased peripheral destruction of platelets. Antibodies coat the platelets, leading to their premature clearance by macrophages in the spleen.

• Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by the classic triad:

  1. Thrombocytopenia (often with small platelets)

  2. Eczema

  3. Immunodeficiency (particularly affecting T cells)

• Patients are prone to recurrent infections and autoimmune disorders.

Other options:

• b) May-Hegglin Anomaly → thrombocytopenia + giant platelets + Döhle-like bodies, no eczema or immunodeficiency

• c) Hermansky-Pudlak syndrome → albinism + platelet storage pool defect, no immunodeficiency or eczema

• d) Scott syndrome → rare bleeding disorder due to platelet membrane defect, no eczema or immunodeficiency

• Hemophilia B, also called Christmas disease, is an X-linked recessive disorder caused by deficiency of factor IX.

• Factor IX is part of the intrinsic coagulation pathway, so patients typically present with:

  • Prolonged aPTT

  • Normal PT

  • Normal platelet count

• Clinical features are similar to Hemophilia A: hemarthroses, deep tissue hematomas, and prolonged bleeding.

Other options:

• a) Factor VIII → Hemophilia A

• c) Factor XI → Hemophilia C (autosomal recessive, milder bleeding)

• d) Factor XIII → rare factor deficiency, causes delayed bleeding, normal PT and aPTT

Von Willebrand disease is the most common inherited bleeding disorder, affecting an estimated 1% of the population. It results from a deficiency or defect in von Willebrand factor (vWF).

Other options:

• a) Hemophilia A → X-linked, less common than vWD

• b) Hemophilia B → X-linked, rarer than Hemophilia A

• d) Factor XI deficiency → rare, more common in certain populations (e.g., Ashkenazi Jews)

• Hemophilia C is a rare autosomal recessive bleeding disorder caused by factor XI deficiency.

• Unlike Hemophilia A and B, Hemophilia C:

  • Usually causes mild bleeding

  • Bleeding often occurs after surgery or trauma, rather than spontaneous hemarthroses

  • aPTT may be prolonged, PT normal

• More common in certain populations, e.g., Ashkenazi Jews.

Other options:

• b) Factor IX → Hemophilia B

• c) Factor VIII → Hemophilia A

• d) Factor XIII → rare deficiency causing delayed bleeding, normal PT/aPTT

• DIC is a condition of widespread activation of coagulation, leading to:

  • Consumption of platelets and coagulation factors

  • Fibrinogen depletion

• Laboratory findings:

  • Prolonged PT and aPTT (both extrinsic and intrinsic pathways affected)

  • Low fibrinogen

  • Thrombocytopenia

  • Elevated D-dimer

Other options:

• a) Hemophilia A → prolonged aPTT only, PT and fibrinogen normal

• b) Hemophilia B → prolonged aPTT only, PT and fibrinogen normal

• d) vWD → may have normal PT, sometimes mild aPTT prolongation; fibrinogen normal

• Mucocutaneous bleeding (e.g., epistaxis, gum bleeding, menorrhagia) is typical of platelet disorders or von Willebrand disease.

• Prolonged bleeding time → suggests platelet function abnormality.

• Low ristocetin-induced platelet aggregation → specifically indicates a defect in von Willebrand factor (vWF), which mediates platelet adhesion via glycoprotein Ib.

Other options:

• Hemophilia A → causes joint/muscle bleeding, normal bleeding time, normal ristocetin test.

• Factor VII deficiency → prolongs PT, not bleeding time or ristocetin aggregation.

• Factor XIII deficiency → causes delayed wound bleeding, normal screening tests.

This patient’s presentation is the classic pentad for TTP:

1. Thrombocytopenia

2. Microangiopathic Hemolytic Anemia (seen on smear as schistocytes)

3. Neurological symptoms (e.g., confusion, headache, seizures)

4. Fever

5. Renal impairment

While the full pentad is not always present, the triad of thrombocytopenia, MAHA, and neurological symptoms is highly specific for TTP.

Why the other options are incorrect:

• a) Idiopathic Thrombocytopenic Purpura (ITP): This is characterized by isolated thrombocytopenia. It does not cause hemolytic anemia or neurological symptoms.

• b) Hemolytic Uremic Syndrome (HUS): HUS also presents with thrombocytopenia and MAHA. However, its hallmark is severe renal failure, and neurological symptoms are less prominent than in TTP. The classic presentation is often preceded by a diarrheal illness.

• d) Heparin-Induced Thrombocytopenia (HIT): HIT causes thrombocytopenia and a high risk of thrombosis (both arterial and venous). It does not typically cause microangiopathic hemolytic anemia or the acute neurological symptoms seen in TTP.

• The patient is post-operative and has normal PT, aPTT, and fibrinogen, but thrombocytopenia (platelet count 40 × 10³/µL).

• This pattern is classic for dilutional thrombocytopenia, which occurs after:

  • Massive transfusions with packed red blood cells or crystalloids

  • Loss of platelets in surgery

• Platelets are diluted more than coagulation factors, leading to low platelet count with otherwise normal coagulation tests.

Other options:

• a) Dilution of coagulation factors → would prolong PT/aPTT, which is normal here.

• b) Intravascular coagulation (DIC) → would show prolonged PT/aPTT, low fibrinogen, and schistocytes.

• c) Hypofibrinogenemia → would reduce fibrinogen, which is normal here.

• Hemophilia A is an X-linked recessive disorder caused by deficiency or dysfunction of factor VIII.

• Factor VIII is part of the intrinsic coagulation pathway, so patients typically show:

  • Prolonged aPTT

  • Normal PT

  • Normal platelet count

• Clinical features include hemarthroses, muscle hematomas, and prolonged bleeding after trauma or surgery.

Other options:

• a) Factor IX → Hemophilia B (Christmas disease)

• c) Factor XI → Hemophilia C

• d) Factor VII → deficiency prolongs PT (extrinsic pathway), not intrinsic

In Polycythemia Vera (PV), a myeloproliferative neoplasm, there is an overproduction of all three blood cell lines (red blood cells, white blood cells, and platelets) by the bone marrow. Therefore, thrombocytosis (an elevated platelet count) is a common characteristic finding.

Other options:

• b) Normal → platelets can be normal in early or mild cases, but typically elevated.

• c) Decreased → uncommon in PV; more typical of bone marrow failure or ITP.

• d) Variable → less precise; in PV, the trend is generally elevated.

• The “large blue cytoplasmic inclusions” described are Döhle-like bodies. These are aggregates of ribosomes and rough endoplasmic reticulum.

• May-Hegglin Anomaly is a rare, inherited platelet disorder characterized by the triad of:

  1. Large, blue, cytoplasmic inclusions (Döhle-like bodies) in neutrophils (and sometimes other white blood cells).

  2. Thrombocytopenia (low platelet count).

  3. Giant platelets.

Why the other options are incorrect:

• a) Wiskott-Aldrich syndrome: This is characterized by small platelets and associated with eczema and immunodeficiency. It does not feature Döhle-like bodies.

• c) Ehlers-Danlos syndrome: This is a connective tissue disorder, not a hematologic disorder, and has no characteristic findings on a blood smear.

• d) Hermansky-Pudlak syndrome: This is a disorder of platelet granules (dense bodies) and albinism. It is associated with platelet storage pool deficiency, not inclusions in white blood cells.

• Factor VIII is primarily produced by endothelial cells (especially in the liver sinusoidal and vascular endothelium), not hepatocytes.

• Other coagulation factors, including VII, IX, X, and most others in the coagulation cascade, are synthesized in the liver.

• Factor VIII circulates bound to von Willebrand factor, which stabilizes it in plasma.

Other options:

• b) Factor IX → produced in the liver

• c) Factor VII → produced in the liver

• d) Factor X → produced in the liver

• Bleeding time measures primary hemostasis, which depends on platelet number, function, and adhesion.

• Both platelet disorders (quantitative or qualitative) and von Willebrand disease (vWD) impair platelet adhesion or aggregation, leading to prolonged bleeding time.

Other options:

• a) PT → measures extrinsic pathway; usually normal in platelet disorders and vWD

• b) aPTT → may be prolonged in some vWD types (severe vWF deficiency) but not in isolated platelet disorders

• d) D-dimer → marker of fibrinolysis; not affected by platelet function or vWD

Ticlopidine and clopidogrel belong to a class of drugs known as P2Y₁₂ ADP receptor antagonists.

• Mechanism: They irreversibly block the P2Y₁₂ subtype of the ADP receptor on the platelet surface.

• Effect: When ADP cannot bind to this receptor, it prevents a key signaling pathway that leads to platelet activation and the conformational change in the GPIIb/IIIa receptor necessary for effective aggregation.

This mechanism is distinct from other antiplatelet drugs:

• Aspirin works by inhibiting the cyclooxygenase enzyme (option d).

• GPIIb/IIIa inhibitors (like Abciximab, Tirofiban, Eptifibatide) directly block the final common pathway of aggregation (option c).

• Drugs that interfere with von Willebrand factor binding are a different class, such as certain monoclonal antibodies (option a).

• Low platelets → suggests a consumption or destruction process.

• Prolonged PT and aPTT → implies deficiency or dysfunction of multiple coagulation factors.

• High D-dimer → indicates intense fibrin formation and breakdown (fibrinolysis).

ITP (a) has low platelets, but PT/aPTT are normal, and D-dimer is not high.
TTP (b) has low platelets, but PT/aPTT are usually normal; D-dimer is not typically very high.
DIC (c) has low platelets, prolonged PT/aPTT (consumption of factors), and high D-dimer due to fibrin degradation products.
Hemophilia A (d) has prolonged aPTT only, platelets and PT are normal, D-dimer not high.

• The most common cause of clinically significant bleeding is thrombocytopenia, i.e., a reduced number of platelets.

• Platelets are essential for primary hemostasis; when their number falls below a critical threshold, patients develop mucocutaneous bleeding such as petechiae, purpura, or epistaxis.

Other options are less common:

• a) Qualitative platelet defects → less frequent; often inherited or drug-induced.

• b & c) Fibrinogen abnormalities → rare; usually present with coagulation defects and deep bleeding rather than common mucosal bleeding.

This syndrome is classically characterized by the triad of:

1. Thrombocytopenia (due to a platelet storage pool defect, specifically a lack of dense granules).

2. Albinism (oculocutaneous albinism).

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

Why the other options are incorrect:

• a) Wiskott-Aldrich syndrome: Characterized by thrombocytopenia (with small platelets), eczema, and immunodeficiency. It is not associated with albinism.

• b) May-Hegglin Anomaly: Characterized by thrombocytopenia (with giant platelets) and Döhle-like bodies in white blood cells. It is not associated with albinism.

• d) Chédiak-Higashi syndrome: This syndrome does involve albinism and is also characterized by recurrent pyogenic infections and giant granules in leukocytes. While it can have a bleeding tendency, it is primarily due to defective platelet aggregation, not consistent thrombocytopenia.

Platelets, or thrombocytes, are produced in the bone marrow and have a relatively short life cycle. They typically circulate in the blood for about 8 to 12 days, with 10 days being the standard average used in medical texts.

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

• Mechanism: The GPIIb/IIIa receptor is the final common pathway for platelet aggregation, as it is responsible for binding fibrinogen and cross-linking platelets. By blocking this receptor, abciximab effectively prevents platelet aggregation.

Why the other options are incorrect:

• a) ADP receptor antagonism: This is the mechanism of drugs like clopidogrel and ticagrelor.

• c) Cyclooxygenase inhibition: This is the mechanism of aspirin.

• d) Phosphodiesterase inhibition: This is the mechanism of dipyridamole and cilostazol.

• Factor XII deficiency (Hageman factor deficiency) is a rare inherited disorder.

• Laboratory findings: markedly prolonged aPTT, but patients are usually asymptomatic and do not have spontaneous bleeding.

• Bleeding may occur only after surgery or trauma, making it a subclinical bleeding disorder.

Other options:

• b) Factor VIII deficiency (Hemophilia A) → spontaneous bleeding, hemarthroses, and prolonged aPTT

• c) Factor IX deficiency (Hemophilia B) → similar to Hemophilia A, spontaneous bleeding common

• d) vWF deficiency → mucocutaneous bleeding, easy bruising, epistaxis, not limited to surgery

• PT measures the extrinsic and common coagulation pathways.

• It primarily evaluates factor VII, which is part of the extrinsic pathway.

• PT is prolonged in conditions such as:

  • Vitamin K deficiency

  • Warfarin therapy

  • Liver disease

  • Factor VII deficiency

Other options:

• a) aPTT → evaluates the intrinsic and common pathways

• c) Thrombin time (TT) → measures conversion of fibrinogen to fibrin

• d) Bleeding time → evaluates platelet function / primary hemostasis

These drugs directly and specifically target receptors on the platelet to prevent aggregation.

• Tirofiban is a glycoprotein IIb/IIIa inhibitor. It directly blocks the final common pathway of platelet aggregation by preventing fibrinogen from binding to the activated GP IIb/IIIa receptor.

Why the other options are incorrect:

The other three drugs are direct anticoagulants, not antiplatelet agents. They work by inhibiting thrombin (Factor IIa) in the coagulation cascade.

• a) Argatroban: A direct thrombin inhibitor (anticoagulant).

• b) Hirudin: A natural direct thrombin inhibitor (anticoagulant) found in leech saliva.

• c) Dabigatran: An oral direct thrombin inhibitor (anticoagulant).

Factor XIII is known as fibrin-stabilizing factor. It cross-links fibrin polymers, forming a stable and strong clot that is more resistant to degradation.

Other options:

• a) Factor VII → part of the extrinsic pathway, initiates coagulation

• c) Factor IX → part of the intrinsic pathway

• d) Factor V → cofactor in the common pathway, accelerates prothrombin conversion

The prothrombin time (PT) test primarily assesses the extrinsic pathway (via tissue factor and factor VII) and the common pathway (factors II, V, X, and fibrinogen).
However, it is most sensitive to the extrinsic pathway because factor VII has the shortest half-life, and the test uses tissue thromboplastin to activate this pathway.

Other options:

• a) Intrinsic pathway → measured by aPTT (factors VIII, IX, XI, XII)

• c) Common pathway → contributes to PT and aPTT, but PT is not solely sensitive to it

• d) Fibrinolytic pathway → not evaluated by PT

• Liver disease impairs synthesis of most coagulation factors (I, II, V, VII, IX, X, XI, XII) because the liver is the primary site of their production.

• Laboratory findings:

  • Prolonged PT → sensitive to factor VII deficiency (short half-life)

  • Prolonged aPTT → deficiency of intrinsic pathway factors

  • Decreased fibrinogen may also occur in advanced disease

• Patients may present with bleeding tendencies, particularly mucocutaneous bleeding.

Other options:

• a) Normal PT and PTT → not typical in significant liver disease

• c) Normal fibrinogen → may be preserved early, but can decrease in advanced disease

• d) Isolated factor VIII deficiency → congenital Hemophilia A, not liver disease

• Vitamin K–dependent coagulation factors require gamma-carboxylation for calcium binding and proper function. These include:

  • Factors II (prothrombin), VII, IX, X

  • Proteins C and S (anticoagulants)

• Factor IX deficiency causes Hemophilia B.

Other options:

• a) Factor VIII → not vitamin K–dependent; deficiency causes Hemophilia A

• c) Factor XI → not vitamin K–dependent; deficiency causes Hemophilia C

• d) Factor XII → not vitamin K–dependent; deficiency usually asymptomatic

Von Willebrand disease is caused by a quantitative deficiency or qualitative defect in von Willebrand factor (vWF).
This factor plays a key role in platelet adhesion and stabilizes factor VIII in the plasma.

Other options:

• a) Platelet receptor deficiency → seen in Bernard-Soulier or Glanzmann thrombasthenia

• c) Factor V deficiency → rare bleeding disorder affecting common pathway

• d) Decreased fibrinogen → affects fibrin clot formation, not vWF

• Factor VIII is part of the intrinsic coagulation pathway.

• Deficiency of factor VIII leads to:

  • Prolonged aPTT (intrinsic pathway affected)

  • Normal PT (extrinsic pathway unaffected)

• This is seen in Hemophilia A.

Other options:

• a) Factor VII → extrinsic pathway → prolonged PT, normal aPTT

• c) Factor X → common pathway → both PT and aPTT prolonged

• d) Factor V → common pathway → both PT and aPTT prolonged

• Unfractionated heparin (UFH) enhances antithrombin III, inhibiting thrombin (factor IIa) and factor Xa.

• aPTT measures the intrinsic and common pathways and is prolonged by heparin, making it the standard test to monitor UFH therapy.

• Therapeutic aPTT is usually 1.5–2.5 times the control.

Other options:

• a) PT → monitors warfarin therapy (extrinsic pathway)

• c) D-dimer → marker of fibrinolysis, not used for monitoring heparin

• d) Bleeding time → assesses platelet function, not heparin effect

Here’s a breakdown of the mechanism:

• Aspirin irreversibly acetylates the enzyme cyclooxygenase-1 (COX-1) within platelets.

• COX-1 is essential for the production of thromboxane A2 (TXA2), a potent promoter of platelet aggregation and vasoconstriction.

• By blocking TXA2 synthesis, aspirin inhibits platelet activation and aggregation for the entire lifespan of the platelet (7-10 days).

Why the other options are incorrect:

• a) Depleting platelet alpha granule content: This is not aspirin’s mechanism. Other conditions or drugs (like proteasome inhibitors) can affect granule release.

• b) Inactivating ADP and phospholipase A2: Aspirin does not directly inactivate ADP. While it affects the arachidonic acid pathway upstream of phospholipase A2, its primary and well-defined target is cyclooxygenase.

• d) Impairing von Willebrand factor: Aspirin does not directly affect von Willebrand factor (vWF). Antibodies or other diseases can impair vWF function.

• Heparin is an anticoagulant that binds to antithrombin III (ATIII) and enhances its activity by ~1000-fold.

• Antithrombin III inactivates:

  • Thrombin (factor IIa)

  • Factor Xa

  • To a lesser extent, factors IXa, XIa, XIIa

• This leads to rapid anticoagulation.

Other options:

• a) Warfarin → vitamin K antagonist, inhibits synthesis of factors II, VII, IX, X

• c) Aspirin → antiplatelet agent, inhibits cyclooxygenase → reduces thromboxane A2

• d) Streptokinase → thrombolytic, activates plasminogen → breaks down fibrin