Hemophilia and Von Willebrand Disease — MCQs
Which of the following statements regarding von Willebrand disease is incorrect?
Bleeding crisis in acute idiopathic thrombo-cytopenic purpura is managed by all except -
Which of the following conditions is least likely to be inherited in a familial manner?
Which of the following is not true regarding Von Willebrand disease?
A 16-year-old adolescent boy with a history of severe hemophilia A is undergoing an elective inguinal hernia repair. Which of the following is the best option for preventing or treating a bleeding complication in the setting of this disease?
A young patient presents with a large retroperitoneal hemorrhage and a history of intermittent knee swelling after strenuous exercise. There is no history of mucosal bleeding. Which of the following clotting factors is primarily deficient in Hemophilia A?
In which of the following conditions is marked bleeding typically observed?
Heavy menstrual bleeding is a common presentation in which of the following? 1. Clotting factor deficiency 2. Fibroid uterus 3. Adenomyosis 4. Prolactinoma.
A 35-year-old lady with normal PT and increased APTT. 2 years back, she was operated for cholecystectomy & did not have any bleeding episode. What is the next investigation for clinical diagnosis?
What does ristocetin testing indicate in von Willebrand disease?
Hemophilia and Von Willebrand Disease Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following statements regarding von Willebrand disease is incorrect?
- A. Type 2 von Willebrand disease is associated with a moderate bleeding tendency.
- B. Type 3 von Willebrand disease is associated with severe deficiency of factor VIII.
- C. Type 1 von Willebrand disease presents with severe bleeding since childhood. (Correct Answer)
- D. Type 2 von Willebrand disease includes subtypes with varying defects in von Willebrand factor.
Explanation: ***Type 1 von Willebrand disease presents with severe bleeding since childhood.*** - This statement is incorrect because **Type 1 von Willebrand disease (vWD)** is characterized by a **partial quantitative deficiency** of von Willebrand factor (vWF), leading to **mild to moderate bleeding** that typically presents later in life or with specific challenges like surgery. - **Severe bleeding since childhood** is more characteristic of **Type 3 vWD**, which involves a near-complete absence of vWF. *Type 2 von Willebrand disease is associated with a moderate bleeding tendency.* - This statement is correct as **Type 2 vWD** involves **qualitative defects** in vWF, meaning the protein is present but doesn't function correctly [1]. - This typically results in a **moderate bleeding tendency**, which can vary depending on the specific subtype (2A, 2B, 2M, 2N). *Type 3 von Willebrand disease is associated with severe deficiency of factor VIII.* - This statement is correct because **Type 3 vWD** is characterized by a near-complete absence of vWF, which is essential for stabilizing **Factor VIII** in circulation [2]. - The severe deficiency of vWF leads to a **marked decrease in Factor VIII levels**, resulting in a bleeding phenotype that can be difficult to distinguish from severe hemophilia A. *Type 2 von Willebrand disease includes subtypes with varying defects in von Willebrand factor.* - This statement is correct as **Type 2 vWD** is subdivided into four main types (2A, 2B, 2M, 2N), each with distinct **qualitative defects** in the von Willebrand factor protein [2]. - These subtypes are differentiated by issues such as **multimerization defects**, increased platelet binding, or decreased affinity for Factor VIII [2].
Question 2: Bleeding crisis in acute idiopathic thrombo-cytopenic purpura is managed by all except -
- A. Intravenous immunoglobulin
- B. Prednisolone
- C. Eltrombopag (Correct Answer)
- D. RhIG
Explanation: ***Eltrombopag*** - **Eltrombopag** is a **thrombopoietin receptor agonist** used for chronic idiopathic thrombocytopenic purpura (ITP) to increase platelet production. - It is **not** used for the immediate management of an acute bleeding crisis, as its effects on platelet counts take several days to manifest. *Intravenous immunoglobulin* - **Intravenous immunoglobulin (IVIG)** works by blocking **Fc receptors** on macrophages, thereby reducing the destruction of antibody-coated platelets. - It is a **first-line treatment** for acute ITP, especially in cases with severe bleeding or very low platelet counts, providing a rapid increase in platelet count. *Prednisolone* - **Prednisolone**, a corticosteroid, is a **first-line treatment** for acute ITP, as it suppresses the immune system and reduces antibody production and platelet destruction. - It helps to quickly raise platelet counts and is effective in managing bleeding episodes, though its effects are not as immediate as IVIG. *RhIG* - **Rh immune globulin (RhIG)** is used in **Rh-positive** patients with ITP to cause a transient hemolytic anemia, which occupies splenic macrophages and reduces platelet destruction. - It `is an effective option` for acute ITP, particularly in patients who require a rapid increase in platelet count and are Rh-positive.
Question 3: Which of the following conditions is least likely to be inherited in a familial manner?
- A. Factor V Leiden mutation (Correct Answer)
- B. Hemophilia
- C. Sickle cell anemia
- D. Acquired thrombotic thrombocytopenic purpura (TTP)
Explanation: ***Thalassemia*** - Thalassemia is a **genetic blood disorder** caused by mutations in hemoglobin genes [1], but biomarkers for diagnosis can sometimes arise **de novo**. - It exhibits **incomplete penetrance** and variable expressivity, meaning not all family members may express the trait despite sharing genes. *Hemophilia* - Hemophilia is a **X-linked recessive** disorder predominantly affecting males, passed from carrier mothers to sons [2]. - The condition leads to **deficiencies in blood clotting factors**, which are inherited in a recognizable familial pattern, though about 30% of patients have no family history due to new mutations [2]. *Factor V Leiden mutation* - Factor V Leiden is an **autosomal dominant** genetic mutation leading to increased clotting risk, often inherited from affected parents. - It presents as a familial tendency towards **venous thromboembolism**, clearly identifying its transmission. *Sickle cell anemia* - Sickle cell anemia is an **autosomal recessive** disorder, requiring two copies of the mutated gene for expression, commonly inherited within families [1]. - It leads to characteristic **sickle-shaped red blood cells**, with a clear familial pattern of inheritance [1]. It is important to distinguish that **hereditary disorders** are by definition transmitted through generations and are therefore **familial**.
Question 4: Which of the following is not true regarding Von Willebrand disease?
- A. Normal platelet count
- B. Quantitative defects are seen in subtypes 1 and 3 von Willebrand disease
- C. Produced by endothelial cells
- D. Hemarthrosis is the usual presentation (Correct Answer)
Explanation: **Hemarthrosis is the usual presentation** - **Hemarthrosis** (bleeding into joints) is characteristic of severe factor deficiencies, such as **hemophilia A or B**, but is uncommon in von Willebrand disease (vWD) [2]. - vWD typically presents with **mucocutaneous bleeding** (e.g., easy bruising, nosebleeds, heavy menstrual bleeding) due to impaired platelet adhesion [2]. *Normal platelet count* - Patients with von Willebrand disease usually have a **normal platelet count**, as the issue is with the function or quantity of **von Willebrand factor (vWF)**, not the number of platelets [3]. - vWF primarily mediates platelet adhesion and protects **factor VIII** from degradation, so platelet production itself is unaffected [1]. *Quantitative defects are seen in subtypes 1 and 3 von Willebrand disease* - **Type 1 vWD** involves a partial **quantitative deficiency** of vWF, meaning reduced levels of otherwise normal vWF. - **Type 3 vWD** is characterized by a severe or near-complete **absence of vWF**, representing the most severe quantitative defect. *Produced by endothelial cells* - **Von Willebrand factor (vWF)** is primarily synthesized and stored in **endothelial cells** (in Weibel-Palade bodies) and also in **megakaryocytes**. - Its production by endothelial cells allows for its release into the bloodstream and subendothelial matrix to facilitate **hemostasis**.
Question 5: A 16-year-old adolescent boy with a history of severe hemophilia A is undergoing an elective inguinal hernia repair. Which of the following is the best option for preventing or treating a bleeding complication in the setting of this disease?
- A. Combination of desmopressin and fresh-frozen plasma
- B. Factor IX concentrate
- C. Fresh-frozen plasma
- D. Combination of ε-aminocaproic acid and desmopressin (Correct Answer)
Explanation: ***Combination of ε-aminocaproic acid and desmopressin*** - For **mild hemophilia A**, **desmopressin** can aid in increasing factor VIII levels temporarily [1]. **ε-aminocaproic acid (EACA)** is an **antifibrinolytic agent** which is useful for mucosal bleeding conditions or as an adjunct during dental procedures or minor surgeries to prevent clot breakdown. - While desmopressin alone may not fully prevent surgical bleeding in hemophilia A, the addition of EACA helps stabilize the clot, reducing the risk of bleeding for minor surgical procedures like inguinal hernia repair [1]. *Combination of desmopressin and fresh-frozen plasma* - **Desmopressin** is useful for **mild hemophilia A** as it releases stored factor VIII [1]. **Fresh-frozen plasma (FFP)** provides all clotting factors. - Using FFP carries a higher risk of **volume overload** and **transfusion-related acute lung injury (TRALI)** compared to factor concentrates or desmopressin alone. *Factor IX concentrate* - **Factor IX concentrate** is used to treat **hemophilia B**, which is a deficiency in factor IX, not factor VIII. - Administering factor IX concentrate to a patient with hemophilia A would not correct their coagulation defect or prevent bleeding [1]. *Fresh-frozen plasma* - While **fresh-frozen plasma (FFP)** contains factor VIII, it is in **non-concentrated amounts**, making it less effective for severe hemophilia A. - FFP also carries a risk of transfusion reactions and **volume overload**, especially when large quantities are needed.
Question 6: A young patient presents with a large retroperitoneal hemorrhage and a history of intermittent knee swelling after strenuous exercise. There is no history of mucosal bleeding. Which of the following clotting factors is primarily deficient in Hemophilia A?
- A. Von Willebrand factor
- B. Lupus anticoagulant
- C. Factor VIII (Correct Answer)
- D. Factor IX
Explanation: ***Factors VIII and IX*** - The symptoms indicate a **hemophilia**, where deficiencies in factors VIII or IX lead to a tendency for **retroperitoneal hemorrhage** and joint swelling, particularly after exercise [1]. - Intermittent swelling of the knees indicates **hemarthrosis**, a common manifestation in hemophilia, supporting the dysfunction of these factors [1]. *Factors XI and XII* - These factors are part of the **intrinsic pathway** but are not primarily associated with **joint bleeding** or sporadic retroperitoneal hemorrhage in young patients. - Deficiencies of these factors typically lead to a milder form of bleeding disorders and not the severe joint symptoms seen here. *Von Willebrand factor* - This factor is crucial for **platelet adhesion** and is associated with **mucosal bleeding**, which is not reported in this patient's history [2]. - The patient's **retroperitoneal hemorrhage** and knee swelling are not characteristic of von Willebrand disease, which typically involves more superficial bleeding [1,2]. *Lupus anticoagulant* - This is an **antiphospholipid antibody** associated with **thrombosis** rather than bleeding, and does not explain the joint swelling or hemorrhagic symptoms. - It leads to a false-positive on coagulation tests and can result in complications like recurrent **thromboembolic events**, rather than bleeding tendencies.
Question 7: In which of the following conditions is marked bleeding typically observed?
- A. Hemophilia A
- B. Hemophilia B
- C. Von Willebrand disease (Correct Answer)
- D. None of the options
Explanation: ***ALL*** - **Acute Lymphoblastic Leukemia (ALL)** often presents with marked **bleeding tendencies** due to thrombocytopenia and bone marrow infiltration. - Patients may experience **petechiae**, **ecchymosis**, and **excessive bleeding** from minor cuts, indicating a serious hematological condition [2]. *VMA disease* - This condition, often referring to **von Willebrand factor deficiency**, may cause bleeding, but usually **not to the extent** seen in ALL [1]. - The bleeding is often more related to **mucosal bleeding** rather than severe hematological compromise as seen in malignancies [1][2]. *Haemophilia B* - Hemophilia B presents with bleeding, but it is typically **mild to moderate** and often related to joint and muscle bleeding [2]. - Patients primarily experience **hemarthrosis** rather than the significant bleeding associated with ALL. *Haemophilia A* - Similar to Hemophilia B, it leads to **bleeding disorders** due to factor VIII deficiency, but the severity is generally **less** than that seen in ALL. - Characteristically, it causes **joint bleeding** and excessive bleeding during surgery, but not generalized bleeding manifestations [2].
Question 8: Heavy menstrual bleeding is a common presentation in which of the following? 1. Clotting factor deficiency 2. Fibroid uterus 3. Adenomyosis 4. Prolactinoma.
- A. 1, 2 and 3 (Correct Answer)
- B. 2, 3 and 4
- C. 1, 2 and 4
- D. 1, 3 and 4
Explanation: ***1, 2 and 3*** - **Clotting factor deficiencies** (e.g., von Willebrand disease, factor XI deficiency) impair normal hemostasis, leading to prolonged and heavy menstrual bleeding. - **Fibroid uterus** causes heavy menstrual bleeding due to increased endometrial surface area, impaired uterine contractility, and dilated underlying vessels. - **Adenomyosis**, characterized by endometrial tissue within the myometrium, leads to an enlarged, boggy uterus and causes heavy and painful menstruation. *2, 3 and 4* - This option correctly identifies fibroid uterus and adenomyosis, which are common causes of heavy menstrual bleeding. - However, **prolactinoma** typically causes **amenorrhea** or oligomenorrhea, not heavy menstrual bleeding, due to its inhibitory effect on gonadotropin-releasing hormone (GnRH). *1, 2 and 4* - While clotting factor deficiency and fibroid uterus are valid causes of heavy menstrual bleeding, **prolactinoma** is an incorrect inclusion. - Prolactinoma often leads to **hypogonadism** and anovulation, resulting in irregular or absent menstrual periods. *1, 3 and 4* - This option includes clotting factor deficiency and adenomyosis, which are causes of heavy menstrual bleeding. - However, **prolactinoma** is not associated with heavy menstrual bleeding; instead, it is known to cause **menstrual irregularities** including amenorrhea.
Question 9: A 35-year-old lady with normal PT and increased APTT. 2 years back, she was operated for cholecystectomy & did not have any bleeding episode. What is the next investigation for clinical diagnosis?
- A. Anti-viper venom assay (Correct Answer)
- B. Factor VIII assay
- C. Ristocetin Cofactor assay
- D. Platelet aggregation test
Explanation: ***Anti-viper venom assay*** - An **isolated prolonged APTT** with a normal PT and no bleeding history, especially in a young woman, strongly suggests **antiphospholipid syndrome (APS)**. [1] - The **dilute Russell's viper venom time (DRVVT)**, often referred to as anti-viper venom assay, is the most common screening test for **lupus anticoagulant**, a key feature of APS. *Factor VIII assay* - While **Factor VIII deficiency** (hemophilia A) causes isolated prolonged APTT, it typically presents with **significant bleeding** (e.g., during surgery) which is absent here. [1] - Furthermore, hemophilia A is an **X-linked recessive** disorder, making its occurrence in a woman less likely unless she is a carrier with extremely low factor levels or has inactivating antibodies. *Ristocetin Cofactor assay* - This assay is used to diagnose **von Willebrand disease (vWD)**, which can present with prolonged APTT. [2] - However, vWD usually causes **mucocutaneous bleeding** and would likely have manifested during a cholecystectomy, which did not occur in this patient. [2] *Platelet aggregation test* - This test evaluates **platelet function** and is used to diagnose disorders like **Glanzmann thrombasthenia** or **Bernard-Soulier syndrome**. - These disorders primarily cause **bleeding** and typically result in a **normal PT and APTT**, with abnormal bleeding time, which doesn't fit the patient's presentation.
Question 10: What does ristocetin testing indicate in von Willebrand disease?
- A. Normal agglutination
- B. Increased agglutination
- C. No agglutination
- D. Decreased agglutination (Correct Answer)
Explanation: ***Decreased agglutination*** - In von Willebrand disease, **ristocetin induces less agglutination** due to a deficiency or dysfunction of von Willebrand factor. - This results in **impaired platelet adhesion** [1], crucial for effective hemostasis. *Increased agglutination* - Would suggest an increased platelet interaction, which is **not characteristic of von Willebrand disease**. - It can occur in conditions with enhanced von Willebrand factor, unlike in this case. *No agglutination* - Suggests complete lack of platelet interaction, which is **not typical** in von Willebrand disease. - There is often some level of interaction, albeit reduced, not a total absence of agglutination. *Normal agglutination* - Indicates no abnormalities, which **contradicts the known pathology** of von Willebrand disease. - Patients typically demonstrate decreased levels of agglutination, not normal findings in this test.
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