Bleeding and Bruising: An MCCQE1 Approach

Introduction

The evaluation of a patient presenting with bleeding or bruising is a high-yield topic for the MCCQE1. As a Canadian medical graduate, you must demonstrate the ability to differentiate between disorders of primary hemostasis (platelet/vessel wall) and secondary hemostasis (coagulation factors).

This guide adheres to the CanMEDS framework, emphasizing the Medical Expert role in diagnosis and management, and the Health Advocate role in recognizing the psychosocial impact of chronic bleeding disorders.

Pathophysiology: The Hemostatic Balance

Understanding the mechanism of bleeding is crucial for interpreting clinical signs.

Clinical Approach to the Bleeding Patient

For MCCQE1 preparation, adopt a structured approach to history and physical examination.

History Taking (The Canadian Context)

Physical Examination

Look for specific dermatological signs that help localize the defect.

Differential Diagnosis

Differentiating between platelet and factor disorders is a core competency.

Investigations

Initial Screen

For any patient with undifferentiated bleeding, order the following. Note the abbreviations used in Canadian hospitals:

1. CBC (Complete Blood Count) + Peripheral Smear
   - Check Platelet count and morphology (clumping, schistocytes).
2. INR (International Normalized Ratio) / PT (Prothrombin Time)
   - Assesses Extrinsic Pathway (Factors VII, X, V, II, Fibrinogen).
3. aPTT (Activated Partial Thromboplastin Time)
   - Assesses Intrinsic Pathway (Factors XII, XI, IX, VIII, X, V, II, Fibrinogen).

Interpretation of Coagulation Studies

• Increased INR only: Warfarin, Vitamin K deficiency (early), Factor VII deficiency.
• Increased aPTT only: Heparin, Hemophilia A (VIII) or B (IX), Von Willebrand Disease (severe), Lupus Anticoagulant.
• Increased INR and aPTT: Liver disease, DIC, Supratherapeutic doses of Warfarin/DOACs, Vitamin K deficiency (late).
• Normal INR/aPTT but bleeding: Von Willebrand Disease (mild/moderate), Platelet function disorders (e.g., Uremia, ASA use), Scurvy (Vitamin C deficiency), Ehlers-Danlos.

Specific Clinical Entities (High Yield)

1. Immune Thrombocytopenia (ITP)

• Pathophysiology: IgG autoantibodies against platelet antigens (GPIIb/IIIa).
• Presentation: Isolated thrombocytopenia in a well-appearing patient. Petechiae/purpura.
• Canadian Management:
  • Children: Usually observe. Spontaneous remission is common.
  • Adults: Treat if platelets <30 or bleeding. First line: Corticosteroids +/- IVIG.

2. Thrombotic Thrombocytopenic Purpura (TTP)

• Pathophysiology: Deficiency of ADAMTS13 enzyme $\rightarrow$ large vWF multimers $\rightarrow$ platelet aggregation/microthrombi.
• Clinical Pentad (FAT RN):
  1. Fever
  2. Anemia (Microangiopathic Hemolytic Anemia - MAHA)
  3. Thrombocytopenia
  4. Renal failure
  5. Neurological symptoms
• Management: Medical Emergency. Plasma Exchange (PLEX). Do NOT give platelets (fuels the fire).

3. Von Willebrand Disease (vWD)

• Epidemiology: Most common inherited bleeding disorder in Canada.
• Pathophysiology: Defective or deficient vWF. vWF adheres platelets to endothelium and carries Factor VIII.
• Labs: Normal/Low Platelets, Increased Bleeding Time/PFA-100, Increased aPTT (if Factor VIII is low enough).
• Treatment: Desmopressin (DDAVP) for Type 1; Factor concentrates containing vWF/FVIII for severe types. Tranexamic acid (antifibrinolytic) is commonly used.

4. Hemophilia A & B

• Genetics: X-linked recessive.
• Hemophilia A: Factor VIII deficiency.
• Hemophilia B: Factor IX deficiency (Christmas Disease).
• Labs: Isolated prolonged aPTT. Corrects with mixing study.
• Treatment: Recombinant factor replacement.

Canadian Guidelines

Choosing Wisely Canada

• Don’t order baseline coagulation studies (INR, aPTT) for patients undergoing low-risk procedures (e.g., cataract surgery, minor skin excision) unless there is a positive bleeding history.
• Don’t order thrombophilia testing (Factor V Leiden, etc.) for adult patients with a first episode of venous thromboembolism (VTE) in the setting of a major transient risk factor (e.g., surgery, trauma).

Thrombosis Canada

• Utilize Thrombosis Canada clinical guides for perioperative management of anticoagulation (bridging vs. stopping). This is a standard resource used by Canadian residents.

Key Points to Remember for MCCQE1

• Hemarthrosis almost always equals Coagulation Factor deficiency (Hemophilia).
• Mucosal bleeding almost always equals Platelet/vWF deficiency.
• Mixing Study: If aPTT corrects with normal plasma, it’s a factor deficiency. If it does not correct, it’s an inhibitor (e.g., Lupus Anticoagulant or Factor VIII inhibitor).
• Vitamin K Dependent Factors: II, VII, IX, X, Protein C, Protein S. (Mnemonic: SNoP 1972 - Seven, Nine, ten, two).
• Warfarin Reversal in Canada: For major bleeding, use Prothrombin Complex Concentrate (PCC) (Octaplex/Beriplex) + Vitamin K IV. FFP is second line.

Study Task List

• Review the coagulation cascade (intrinsic vs extrinsic).
• Memorize the “FAT RN” pentad for TTP.
• Practice interpreting mixing studies.
• Review the mechanism of action of DOACs vs Warfarin.
• Understand the role of Tranexamic Acid in menorrhagia and trauma.

Sample Question

Clinical Scenario

A 24-year-old woman presents to her family physician complaining of heavy menstrual periods since menarche. She reports that she has to change her pad every 2 hours on the heaviest days. She also notes frequent nosebleeds that take a long time to stop and prolonged bleeding after a wisdom tooth extraction last year. She takes no medications. Her maternal aunt has similar symptoms.

Physical examination reveals scattered petechiae on her lower legs but no joint swelling or deformities.

Laboratory investigations:

• Hemoglobin: 110 g/L (Normal: 120–160)
• Platelet count: 250 x 10^9/L (Normal: 150–400)
• INR: 1.0 (Normal: 0.9–1.2)
• aPTT: 42 s (Normal: 25–35)

Question

Which one of the following is the most likely diagnosis?

Options

• A. Immune Thrombocytopenia (ITP)
• B. Hemophilia A
• C. Von Willebrand Disease
• D. Vitamin K Deficiency
• E. Factor V Leiden Mutation

Explanation

The correct answer is:

• C. Von Willebrand Disease

Detailed Explanation: This clinical scenario is classic for Von Willebrand Disease (vWD), the most common inherited bleeding disorder.

• Clinical Clues: The patient has mucocutaneous bleeding (menorrhagia, epistaxis) and a history of post-procedural bleeding (dental extraction). This points toward a defect in primary hemostasis. The family history (maternal aunt) suggests an autosomal dominant inheritance pattern, which is typical for vWD (specifically Type 1).
• Lab Interpretation:
  • Platelet count: Normal. This makes thrombocytopenia (ITP) unlikely.
  • INR: Normal. This rules out extrinsic pathway defects and significant Vitamin K deficiency.
  • aPTT: Mildly prolonged (42s). vWF acts as a carrier protein for Factor VIII, protecting it from degradation. In vWD, Factor VIII levels can be low, leading to a prolonged aPTT. However, the aPTT can also be normal in milder cases.
  • Hemoglobin: Mild anemia likely due to menorrhagia.

Why other options are incorrect:

• A. Immune Thrombocytopenia (ITP): Would present with a low platelet count.
• B. Hemophilia A: While this causes Factor VIII deficiency and prolonged aPTT, it is X-linked recessive. It is extremely rare in females (requires a carrier mother and affected father, or Lyonization effects). Furthermore, Hemophilia typically presents with deep tissue bleeding (hemarthrosis), not just mucocutaneous bleeding.
• D. Vitamin K Deficiency: Would prolong both the INR and aPTT (affects factors II, VII, IX, X). The normal INR makes this incorrect.
• E. Factor V Leiden: This is a pro-thrombotic (hypercoagulable) state, not a bleeding disorder. It leads to DVTs and PEs.

References

1. Medical Council of Canada. (n.d.). MCCQE Part I Clinical Decision-Making and Multiple-Choice Question Objectives.
2. Thrombosis Canada. (2023). Clinical Guides: Bleeding Management. Retrieved from Thrombosis Canada .
3. Choosing Wisely Canada. (2023). Hematology: Five Things Physicians and Patients Should Question. Retrieved from Choosing Wisely Canada .
4. Kaushansky, K., et al. (2021). Williams Hematology (10th ed.). McGraw Hill.
5. Sabatine, M. S. (2020). Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (7th ed.). Wolters Kluwer. (Adapted for Canadian Reference).