Explanation:

• A. Leuco-erythroblastic blood picture is present: Correct. A leucoerythroblastic blood film (presence of immature red and white cells) is characteristic of primary myelofibrosis due to marrow fibrosis and extramedullary haematopoiesis. (Essential Haematology, 6th Edition, p. 211, Table 8.3).
• B. Splenomegaly is present: Correct. Splenomegaly, often massive, is a cardinal feature resulting from extramedullary haematopoiesis. (Essential Haematology, 6th Edition, p. 210).
• C. Generalized lymphadenopathy present: Incorrect. Generalized lymphadenopathy is not a typical feature of primary myelofibrosis.
• D. JAK 2 mutation present in 50%: Correct. The JAK2 V617F mutation is found in approximately 50% of patients with primary myelofibrosis. (Essential Haematology, 6th Edition, p. 210).
• E. Regular transfusions are required: Correct. Anaemia is a major problem, and many patients become transfusion-dependent as the disease progresses. (Essential Haematology, 6th Edition, p. 211).

References:

• Hoffbrand A.V., Moss P.A.H. (2011) Essential Haematology, 6th Edition. Wiley-Blackwell.

Explanation: The patient presents with signs of bleeding and sepsis (fever). The coagulation profile shows significantly prolonged Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and Thrombin Time (TT), along with markedly low Fibrinogen levels.

• A. Acute hepatic failure: Incorrect. While severe liver failure can cause prolonged PT, APTT, and low fibrinogen due to decreased synthesis, the TT is often less affected or normal unless dysfibrinogenemia is present. Bleeding can occur, but this extreme profile, especially the very low fibrinogen and prolonged TT, is more suggestive of consumption.
• B. Disseminated intravascular coagulation (DIC): Correct. DIC involves systemic activation of coagulation, leading to widespread fibrin deposition and consumption of coagulation factors (prolonging PT, APTT, TT) and platelets (thrombocytopenia, although platelet count not given here). Fibrinogen is consumed, leading to low levels. This pattern is highly characteristic of DIC, often triggered by sepsis (fever). (Essential Haematology, 6th Edition, p. 355-358, Table 26.6).
• C. Factor XIII deficiency: Incorrect. Factor XIII deficiency results in unstable clots and delayed bleeding, but PT, APTT, TT, and fibrinogen levels are normal.
• D. Warfarin overdose: Incorrect. Warfarin overdose primarily prolongs the PT (and INR) significantly. APTT may be prolonged, but TT and fibrinogen levels are typically normal.
• E. Factor VIII deficiency: Incorrect. Factor VIII deficiency (Haemophilia A) causes an isolated prolongation of the APTT. PT, TT, and fibrinogen levels are normal.

References:

• Hoffbrand A.V., Moss P.A.H. (2011) Essential Haematology, 6th Edition. Wiley-Blackwell.

Explanation: The coagulation profile shows prolonged Activated Partial Thromboplastin Time (APTT) and prolonged Bleeding Time (BT), with normal Prothrombin Time (PT) and Thrombin Time (TT).

• A. Disseminated intravascular coagulation (DIC): Incorrect. DIC typically causes prolonged PT, APTT, and TT, low fibrinogen, and low platelets. BT is usually normal unless thrombocytopenia is severe.
• B. Factor XIII deficiency: Incorrect. Factor XIII deficiency affects fibrin clot stabilization. Screening tests (PT, APTT, TT, BT, platelet count) are typically normal. Diagnosis requires a specific clot solubility test.
• C. Haemophilia A: Incorrect. Haemophilia A (Factor VIII deficiency) causes a prolonged APTT because Factor VIII is in the intrinsic pathway. PT, TT, and BT are normal.
• D. Haemophilia B: Incorrect. Haemophilia B (Factor IX deficiency) also causes a prolonged APTT (intrinsic pathway) with normal PT, TT, and BT.
• E. von Willebrand disease (vWD): Correct. vWD involves deficient or dysfunctional von Willebrand Factor (vWF). vWF is needed for platelet adhesion (prolonged BT) and stabilizes Factor VIII (prolonged APTT). PT and TT are normal. This pattern fits the presented results and is a common cause of menorrhagia in young females. (Essential Haematology, 6th Edition, p. 352-353, Table 26.2).

References:

• Hoffbrand A.V., Moss P.A.H. (2011) Essential Haematology, 6th Edition. Wiley-Blackwell.

Explanation: The key findings are a prolonged Activated Partial Thromboplastin Time (APTT) and a prolonged Bleeding Time (BT), with normal Prothrombin Time (PT) and Thrombin Time (TT).

• A. Disseminated intravascular coagulation (DIC): Incorrect. DIC typically involves consumption of multiple factors and platelets, leading to prolonged PT, APTT, and TT, low fibrinogen, low platelets, and often a normal or secondarily prolonged BT. This pattern doesn’t match. (Essential Haematology, 6th Edition, Table 26.6, p. 357-358).
• B. Immune thrombocytopenia (ITP): Incorrect. ITP is characterized by isolated thrombocytopenia (low platelet count). Coagulation times (PT, APTT, TT) are typically normal. Bleeding time would be prolonged due to low platelets, but the normal coagulation screen excludes this as the sole cause. (Essential Haematology, 6th Edition, p. 334-336).
• C. Liver disease: Incorrect. Severe liver disease impairs synthesis of multiple coagulation factors (II, VII, IX, X, V, fibrinogen) and would prolong PT, APTT, and potentially TT. Bleeding time may be prolonged due to associated thrombocytopenia or platelet dysfunction, but this isolated APTT/BT prolongation pattern is not typical. (Essential Haematology, 6th Edition, p. 355, Table 26.4).
• D. von Willebrand disease (vWD): Correct. vWD involves deficiency or dysfunction of von Willebrand Factor (vWF). vWF is crucial for platelet adhesion (affecting BT) and acts as a carrier for Factor VIII. Reduced Factor VIII levels prolong the APTT (intrinsic pathway). PT and TT are typically normal. This pattern perfectly matches the results provided. (Essential Haematology, 6th Edition, p. 352-353, Table 26.2).
• E. Warfarin therapy: Incorrect. Warfarin inhibits vitamin K-dependent factors (II, VII, IX, X), primarily prolonging the PT (monitored by INR). APTT may be slightly prolonged at high INR but is not the primary test affected. TT and BT are typically normal. (Essential Haematology, 6th Edition, p. 374-375).

Conclusion: The combination of prolonged APTT and prolonged Bleeding Time with normal PT and TT is characteristic of von Willebrand disease.

References:

• Hoffbrand A.V., Moss P.A.H. (2011) Essential Haematology, 6th Edition. Wiley-Blackwell.

Explanation:

• A. Anti thrombin deficiency is an inherited disorder: Correct. Antithrombin deficiency is an autosomal dominant inherited condition that increases the risk of venous thrombosis (Essential Haematology, 6th Edition, p. 367).
• B. Antiphospholipid antibody syndrome presents as recurrent first trimester abortions: Correct. Antiphospholipid syndrome (APS) is associated with both venous and arterial thrombosis and/or recurrent miscarriage. While miscarriage can occur at any stage, it’s a known association (Essential Haematology, 6th Edition, p. 369-370, Table 27.3).
• C. Inherited causes are more common than acquired: Incorrect. Acquired risk factors for thrombosis (e.g., surgery, malignancy, immobility, certain medications, inflammatory conditions) are generally more common in the population than inherited thrombophilias, although inherited factors contribute significantly to risk, especially in younger individuals or those with recurrent events (Essential Haematology, 6th Edition, p. 364, Table 27.2).
• D. Protein C is a naturally occurring anticoagulant: Correct. Protein C, along with Protein S, is a vitamin K-dependent naturally occurring anticoagulant that inactivates factors Va and VIIIa (Essential Haematology, 6th Edition, p. 325). Deficiency is an inherited cause of thrombophilia (p. 367).
• E. Protein S is a vitamin K dependent anticoagulant: Correct. Protein S acts as a cofactor for activated protein C and is also vitamin K-dependent. Its deficiency is also an inherited cause of thrombophilia (Essential Haematology, 6th Edition, p. 325, 367).

References:

• Hoffbrand A.V., Moss P.A.H. (2011) Essential Haematology, 6th Edition. Wiley-Blackwell.