# Clinical Cases: Bleeding Disorders

## Case 1: Immune Thrombocytopenia (ITP)

### Patient Presentation
**Demographics:** 28-year-old female

**Chief Complaint:** Easy bruising and petechiae for 2 weeks

**History of Present Illness:**
The patient noticed increasing bruising on her extremities over the past 2 weeks, occurring with minimal or no trauma. She also developed a petechial rash on her lower legs. She reports heavier than usual menstrual periods this cycle. She had a viral upper respiratory infection approximately 3 weeks ago that resolved spontaneously. She denies any fever, weight loss, bone pain, or other systemic symptoms. She takes no regular medications and has no history of bleeding disorders.

**Physical Examination:**
- Vital signs: BP 118/72, HR 78, RR 14, Temp 36.8C
- General: Well-appearing young woman
- Skin: Multiple ecchymoses on arms and legs; petechial rash on lower extremities
- HEENT: No gingival bleeding, no lymphadenopathy
- Cardiac: Regular rhythm, no murmurs
- Abdomen: Soft, non-tender, no hepatosplenomegaly
- Neurologic: Normal

### Workup and Results

**Complete Blood Count:**
- WBC: 7,200/uL (normal differential)
- Hemoglobin: 12.8 g/dL (normal)
- Platelets: 8,000/uL (severely low)
- MCV: 88 fL (normal)

**Peripheral Blood Smear:**
- Markedly decreased platelets
- Large platelets (megathrombocytes) visible
- Normal RBC and WBC morphology
- No schistocytes or blasts

**Additional Labs:**
- PT/INR: 12.5 sec / 1.0 (normal)
- aPTT: 28 sec (normal)
- Fibrinogen: 285 mg/dL (normal)
- LDH: 180 U/L (normal)
- HIV, HCV: Negative

### Clinical Image

![Immune Thrombocytopenia Blood Smear](case_01_image.jpg)

*Peripheral blood smear in immune thrombocytopenia showing markedly reduced platelet count with large platelets (megathrombocytes) indicating increased bone marrow production in response to peripheral destruction.*

### Diagnosis
**Primary Immune Thrombocytopenia (ITP)**

Diagnostic criteria:
- Isolated thrombocytopenia (<100,000/uL) with no other cause identified
- Normal or increased platelet size (young platelets)
- Normal RBC and WBC morphology
- Negative secondary workup (HIV, HCV)
- No splenomegaly
- Post-viral trigger common in young adults

### Treatment Plan
1. **First-line therapy:**
   - Prednisone 1 mg/kg/day for 2-4 weeks with taper
   - Or dexamethasone 40 mg daily x 4 days

2. **Adjunctive measures:**
   - Avoid aspirin, NSAIDs, and anticoagulants
   - Activity restrictions to prevent trauma

3. **If severe bleeding or refractory:**
   - IVIG 1 g/kg x 1-2 doses (rapid but temporary effect)
   - Anti-D immunoglobulin (if Rh-positive)

4. **Second-line options if needed:**
   - Thrombopoietin receptor agonists (romiplostim, eltrombopag)
   - Rituximab
   - Splenectomy (third-line)

### Teaching Points
1. ITP is a diagnosis of exclusion - other causes of thrombocytopenia must be ruled out
2. Large platelets suggest increased bone marrow production in response to peripheral destruction
3. The mechanism involves antiplatelet antibodies (often anti-GPIIb/IIIa) causing splenic destruction
4. Primary ITP has no identifiable cause; secondary ITP occurs with underlying conditions
5. Treatment is based on platelet count and bleeding symptoms, not just the number
6. Many patients with platelets >30,000/uL require no treatment if asymptomatic

---

## Case 2: Hemophilia A with Hemarthrosis

### Patient Presentation
**Demographics:** 12-year-old male

**Chief Complaint:** Acute right knee swelling and pain for 8 hours

**History of Present Illness:**
The patient was playing soccer when he felt sudden pain in his right knee. The knee became progressively swollen over several hours. He has known severe hemophilia A diagnosed in infancy and has had previous hemarthrosis episodes affecting his left elbow and ankles. He is on prophylactic factor VIII replacement but missed his last two scheduled doses. His maternal uncle also has hemophilia.

**Physical Examination:**
- Vital signs: BP 108/65, HR 92, RR 18, Temp 37.0C, weight 40 kg
- General: Boy in moderate distress due to pain
- Right knee: Markedly swollen, warm, tender; held in flexion; unable to fully extend
- Left elbow: Chronic changes with limited range of motion from prior hemarthrosis
- Skin: No petechiae or purpura
- Abdomen: No hepatosplenomegaly

### Workup and Results

**Complete Blood Count:**
- WBC: 8,400/uL
- Hemoglobin: 11.8 g/dL
- Platelets: 285,000/uL

**Coagulation Studies:**
- PT/INR: 12.8 sec / 1.0 (normal)
- aPTT: 72 sec (prolonged; normal 25-35 sec)
- Fibrinogen: 310 mg/dL (normal)

**Factor Assays:**
- Factor VIII activity: <1% (severe deficiency)
- Factor IX activity: 95% (normal)
- von Willebrand factor antigen: 105% (normal)

**Mixing Study:**
- aPTT corrects with 1:1 mix with normal plasma

### Clinical Image

![Hemophilic Arthropathy](case_01_image.jpg)

*Clinical photograph and radiograph demonstrating acute hemarthrosis with joint swelling and effusion, alongside chronic hemophilic arthropathy changes from recurrent bleeding episodes.*

### Diagnosis
**Severe Hemophilia A with Acute Hemarthrosis**

Key features:
- X-linked recessive inheritance (family history)
- Severe disease: Factor VIII <1%
- Prolonged aPTT with normal PT (intrinsic pathway defect)
- aPTT corrects with mixing study (factor deficiency, not inhibitor)
- Characteristic deep tissue bleeding pattern

### Treatment Plan
1. **Acute hemarthrosis treatment:**
   - Recombinant factor VIII replacement
   - Target factor level: 40-60% initially
   - Dose calculation: Weight (kg) x desired % rise x 0.5 = units
   - For this patient: 40 kg x 50 x 0.5 = 1,000 units
   - Repeat in 24 hours, continue until bleeding resolved

2. **Joint management:**
   - Rest, ice, compression, elevation (RICE)
   - Immobilization initially, then early mobilization
   - Physical therapy after acute phase resolves

3. **Long-term management:**
   - Resume prophylactic factor VIII (25-40 IU/kg 3x weekly)
   - Consider emicizumab for prophylaxis
   - Education about adherence
   - Monitor for inhibitor development

4. **Avoid:**
   - Aspirin and NSAIDs (use acetaminophen for pain)
   - Intramuscular injections
   - High-risk contact sports

### Teaching Points
1. Hemophilia A (factor VIII deficiency) is X-linked recessive, affecting males with carrier females
2. Severity classification: severe <1%, moderate 1-5%, mild 5-40% factor activity
3. The characteristic bleeding pattern is deep tissue: hemarthrosis, muscle hematomas, delayed post-surgical bleeding
4. aPTT is prolonged while PT remains normal (factor VIII is in intrinsic pathway only)
5. Mixing studies correct in deficiency but not in presence of inhibitors
6. Prophylaxis prevents joint damage and is now standard of care for severe hemophilia
7. Emicizumab (bispecific antibody mimicking factor VIII) has transformed prophylaxis

---

## Case 3: von Willebrand Disease Type 1

### Patient Presentation
**Demographics:** 22-year-old female

**Chief Complaint:** Referral for evaluation of heavy menstrual bleeding and easy bruising

**History of Present Illness:**
The patient reports lifelong heavy menstrual periods requiring 8-10 pads per day during peak flow, lasting 7-8 days. She has been diagnosed with iron deficiency anemia and has required iron supplementation since adolescence. She also reports easy bruising and prolonged bleeding after dental extraction last year requiring packing. She has had one episode of significant epistaxis requiring emergency department evaluation. Her mother has similar bleeding symptoms. She has never undergone major surgery.

**Physical Examination:**
- Vital signs: BP 112/68, HR 82, RR 14, Temp 36.9C
- General: Healthy-appearing young woman
- Skin: Several ecchymoses on extremities
- HEENT: No active epistaxis, no oral petechiae
- Cardiac: Normal
- Abdomen: No hepatosplenomegaly

### Workup and Results

**Complete Blood Count:**
- WBC: 6,800/uL
- Hemoglobin: 10.2 g/dL (low; iron deficiency)
- MCV: 76 fL (microcytic)
- Platelets: 245,000/uL

**Iron Studies:**
- Ferritin: 8 ng/mL (low)
- Iron saturation: 12% (low)

**Coagulation Studies:**
- PT/INR: 12.2 sec / 1.0 (normal)
- aPTT: 38 sec (high-normal to mildly prolonged)

**von Willebrand Panel:**
- vWF antigen: 32% (low; normal 50-150%)
- vWF activity (ristocetin cofactor): 28% (low)
- Factor VIII activity: 38% (low)
- vWF multimer analysis: Normal distribution

**Blood Type:** Type O (lower baseline vWF)

### Diagnosis
**von Willebrand Disease Type 1**

Diagnostic criteria:
- Reduced vWF antigen and activity (proportionate reduction)
- Mucocutaneous bleeding pattern (menorrhagia, bruising, epistaxis)
- Positive family history (autosomal dominant)
- Factor VIII mildly reduced (vWF is carrier for FVIII)
- Normal multimer pattern
- Blood type O (naturally lower vWF levels)

### Treatment Plan
1. **DDAVP trial:**
   - Test response with DDAVP (desmopressin) infusion
   - Expected 2-5 fold increase in vWF and FVIII
   - If adequate response, can use for bleeding or procedures

2. **Menorrhagia management:**
   - Combined oral contraceptives (increase vWF levels)
   - Tranexamic acid during menses
   - Iron supplementation to correct anemia

3. **For procedures/bleeding:**
   - DDAVP intranasal (Stimate) or IV before procedures
   - vWF concentrate if DDAVP-unresponsive or contraindicated
   - Antifibrinolytics (tranexamic acid) as adjunct

4. **Avoidance:**
   - Aspirin and NSAIDs
   - Provide documentation for emergency situations

5. **Family counseling:**
   - Autosomal dominant inheritance
   - Offer testing to family members

### Teaching Points
1. von Willebrand disease is the most common inherited bleeding disorder (~1% prevalence)
2. vWF has dual function: platelet adhesion AND factor VIII carrier protein
3. Type 1 (70-80% of cases) is partial quantitative deficiency with proportional reduction
4. Mucocutaneous bleeding pattern reflects the primary hemostatic role of vWF
5. DDAVP releases endothelial stores and is effective for type 1 and most type 2 variants
6. DDAVP is contraindicated in type 2B (may worsen thrombocytopenia)
7. Type O blood is associated with lower baseline vWF levels
8. Testing should be performed when patient is not stressed, inflamed, or pregnant