# Clinical Cases: Thrombotic Disorders

## Case 1: Deep Vein Thrombosis and Pulmonary Embolism

### Patient Presentation
**Demographics:** 58-year-old male

**Chief Complaint:** Left leg swelling and sudden shortness of breath

**History of Present Illness:**
The patient noticed progressive left leg swelling and calf pain over the past 5 days. Today, he developed sudden onset of shortness of breath and mild chest discomfort. He underwent right knee replacement surgery 3 weeks ago and has been relatively immobile since then. He has no prior history of blood clots. He takes lisinopril for hypertension. He denies hemoptysis but reports mild pleuritic chest pain.

**Physical Examination:**
- Vital signs: BP 135/85, HR 108, RR 24, Temp 37.2C, SpO2 92% on room air
- General: Anxious male in mild respiratory distress
- Lungs: Clear to auscultation, tachypneic
- Cardiac: Tachycardic, regular rhythm, loud P2
- Left leg: Significant edema from foot to mid-thigh, warmth, tenderness along femoral vein course
- Right leg: Post-surgical changes, no acute swelling

### Workup and Results

**Laboratory:**
- D-dimer: 4,850 ng/mL (markedly elevated; normal <500)
- Troponin I: 0.15 ng/mL (mildly elevated)
- BNP: 450 pg/mL (elevated)

**Arterial Blood Gas:**
- pH 7.46, pCO2 32 mmHg, pO2 68 mmHg on room air

**Imaging:**
- Compression ultrasound left leg: Non-compressible femoral and popliteal veins with echogenic thrombus
- CT pulmonary angiography: Bilateral pulmonary emboli involving segmental and subsegmental branches; RV/LV ratio 1.2

**ECG:**
- Sinus tachycardia, S1Q3T3 pattern, T-wave inversions in V1-V3

### Clinical Image

![CT Pulmonary Angiography](case_01_image.jpg)

*CT pulmonary angiography demonstrating filling defects (arrows) in the pulmonary arteries consistent with acute pulmonary embolism, with evidence of right ventricular strain.*

### Diagnosis
**Proximal Deep Vein Thrombosis with Submassive Pulmonary Embolism**

Key features:
- Provoked VTE (recent surgery with immobilization)
- Proximal DVT (femoral and popliteal involvement)
- Submassive PE (RV dysfunction but hemodynamically stable)
- Elevated biomarkers indicating cardiac strain

### Treatment Plan
1. **Immediate anticoagulation:**
   - Initiate therapeutic anticoagulation with LMWH or DOAC
   - Consider rivaroxaban 15 mg BID x 21 days, then 20 mg daily
   - Or apixaban 10 mg BID x 7 days, then 5 mg BID

2. **Monitoring:**
   - Close hemodynamic monitoring given submassive classification
   - Serial echocardiography to assess RV function
   - Consider ICU admission for first 24-48 hours

3. **Duration of therapy:**
   - 3 months minimum (provoked by transient risk factor)
   - Reassess at 3 months; likely can discontinue given clear provocation

4. **Supportive care:**
   - Supplemental oxygen
   - Graduated compression stockings for DVT

5. **Not indicated:**
   - Systemic thrombolysis (reserved for massive PE with hemodynamic instability)
   - IVC filter (no contraindication to anticoagulation)

### Teaching Points
1. Virchow's triad explains VTE risk: stasis (immobility), endothelial injury (surgery), hypercoagulability
2. D-dimer is sensitive but not specific; useful to exclude VTE in low-probability patients
3. Submassive PE has RV dysfunction but stable hemodynamics; massive PE has hypotension
4. The S1Q3T3 pattern and anterior T-wave inversions suggest right heart strain
5. Provoked VTE (by transient risk factor) has lower recurrence risk than unprovoked VTE
6. DOACs are now first-line for most VTE; advantages include fixed dosing and fewer interactions

---

## Case 2: Antiphospholipid Syndrome

### Patient Presentation
**Demographics:** 32-year-old female

**Chief Complaint:** Left leg swelling and history of recurrent pregnancy losses

**History of Present Illness:**
The patient presents with 4 days of progressive left leg swelling and pain. She has a history of three first-trimester pregnancy losses and one stillbirth at 24 weeks gestation. She had a "blood clot" 5 years ago in her arm associated with a central line during hospitalization for pneumonia, for which she received 3 months of anticoagulation. She is otherwise healthy and takes no medications.

**Physical Examination:**
- Vital signs: BP 125/78, HR 84, RR 16, Temp 36.9C
- General: Healthy-appearing woman
- Cardiovascular: Regular rhythm, no murmurs
- Left leg: Pitting edema to knee, calf tenderness, positive Homan's sign
- Right leg: Normal
- Skin: Livedo reticularis pattern on lower extremities

### Workup and Results

**Compression Ultrasound:**
- Left popliteal and posterior tibial vein thrombosis confirmed

**Coagulation Studies:**
- PT/INR: 12.5 sec / 1.0
- aPTT: 52 sec (prolonged; normal 25-35)
- Mixing study: Does NOT correct (46 sec after mix)

**Antiphospholipid Antibody Panel:**
- Lupus anticoagulant: Positive (dRVVT ratio 2.1)
- Anticardiolipin IgG: 85 GPL (high positive; normal <20)
- Anti-beta-2-glycoprotein I IgG: 78 SGU (high positive)

**Additional Labs:**
- ANA: Positive 1:80 (low titer)
- Anti-dsDNA: Negative
- CBC: Normal

### Clinical Image

![Livedo Reticularis](case_01_image.jpg)

*Clinical photograph demonstrating livedo reticularis, a lace-like violaceous skin pattern commonly seen in antiphospholipid syndrome, resulting from microvascular blood flow abnormalities.*

### Diagnosis
**Antiphospholipid Syndrome (Primary)**

Diagnostic criteria met:
- Clinical criteria: Vascular thrombosis (2 events) AND obstetric morbidity (recurrent early losses, one late fetal loss)
- Laboratory criteria: Triple-positive (LA, aCL, anti-B2GPI all positive)
- Confirmation required: Repeat testing at 12+ weeks to confirm persistence

### Treatment Plan
1. **Acute DVT treatment:**
   - Therapeutic anticoagulation with warfarin (INR target 2.0-3.0)
   - Bridge with LMWH until INR therapeutic for 2 days
   - Note: DOACs are generally NOT recommended for APS (especially triple-positive)

2. **Duration:**
   - Indefinite anticoagulation given:
     - Recurrent thrombosis
     - Triple-positive antibodies (highest risk)
     - Obstetric APS

3. **Future pregnancy management:**
   - When pregnancy desired: LMWH + low-dose aspirin throughout pregnancy
   - Close obstetric monitoring
   - Avoid warfarin in pregnancy (teratogenic)

4. **Confirm diagnosis:**
   - Repeat antiphospholipid antibodies at 12+ weeks
   - Must remain positive to confirm diagnosis

5. **Lupus evaluation:**
   - Monitor for development of SLE (currently no criteria met)

### Teaching Points
1. APS is characterized by thrombosis AND/OR pregnancy morbidity with persistent antiphospholipid antibodies
2. Lupus anticoagulant prolongs aPTT in vitro but causes thrombosis in vivo (paradox)
3. Triple-positive patients (all 3 antibody types) have highest thrombosis risk
4. Warfarin is preferred over DOACs for APS, especially if triple-positive or arterial events
5. Laboratory diagnosis requires positivity on 2 occasions at least 12 weeks apart
6. Catastrophic APS is rapid-onset multi-organ failure requiring urgent plasmapheresis and anticoagulation
7. Primary APS occurs without underlying disease; secondary APS is associated with SLE or other autoimmune conditions

---

## Case 3: Heparin-Induced Thrombocytopenia

### Patient Presentation
**Demographics:** 67-year-old male

**Chief Complaint:** Leg pain and declining platelet count during hospitalization

**History of Present Illness:**
The patient is hospitalized following coronary artery bypass grafting (CABG) 8 days ago. He has been receiving unfractionated heparin for DVT prophylaxis since admission. Today, nursing noted he has new left calf swelling and pain. Review of labs shows his platelet count has fallen from a post-operative baseline of 180,000/uL to 62,000/uL today (65% decline over 4 days). He has no bleeding symptoms.

**Physical Examination:**
- Vital signs: BP 138/82, HR 88, RR 16, Temp 37.4C
- General: Post-operative male, appropriate recovery
- Cardiovascular: Healing sternotomy, regular rhythm
- Left leg: Swelling, warmth, calf tenderness
- Skin: No petechiae or ecchymoses; IV site erythema at previous heparin infusion site

### Workup and Results

**Laboratory Trends:**
| Day | Platelets |
|-----|-----------|
| Post-op day 1 | 145,000/uL |
| Post-op day 3 | 180,000/uL |
| Post-op day 5 | 125,000/uL |
| Post-op day 7 | 85,000/uL |
| Post-op day 8 | 62,000/uL |

**4Ts Score:**
- Thrombocytopenia: 2 points (50-70% fall)
- Timing: 2 points (day 5-10 of heparin)
- Thrombosis: 2 points (new DVT confirmed)
- Other causes: 2 points (no other obvious cause)
- Total: 8 points (HIGH probability)

**HIT Testing:**
- Anti-PF4/heparin ELISA: Positive (OD 2.1)
- Serotonin release assay: Positive (95% release)

**Imaging:**
- Compression ultrasound: Left popliteal vein DVT confirmed

### Clinical Image

![Platelet Count Trend in HIT](case_01_image.jpg)

*Graph showing characteristic platelet count decline in heparin-induced thrombocytopenia, typically occurring 5-10 days after heparin initiation with greater than 50% fall from baseline.*

### Diagnosis
**Heparin-Induced Thrombocytopenia (HIT) Type II with DVT**

Diagnostic criteria:
- Timing: Platelet decline days 5-10 after heparin exposure
- Magnitude: >50% fall from post-operative peak
- Thrombosis: New DVT despite prophylaxis
- High 4Ts score (8 points)
- Laboratory confirmation with positive ELISA and SRA

### Treatment Plan
1. **Immediate actions:**
   - STOP ALL HEPARIN (including flushes, heparin-coated catheters)
   - Document HIT allergy in medical record

2. **Alternative anticoagulation:**
   - Start argatroban (direct thrombin inhibitor) IV infusion
   - Target aPTT 1.5-3x baseline
   - Continue until platelets recover >150,000/uL

3. **Transition to long-term anticoagulation:**
   - Once platelets >150,000/uL, may transition to warfarin
   - Overlap argatroban with warfarin for 5+ days
   - INR target 2.0-3.0
   - Duration: Minimum 3 months for HIT with thrombosis

4. **Do NOT:**
   - Transfuse platelets (may worsen thrombosis)
   - Use LMWH (cross-reacts with HIT antibodies)
   - Start warfarin before platelet recovery (risk of limb gangrene)

5. **Future precautions:**
   - Lifetime avoidance of heparin
   - HIT antibodies wane after ~100 days but re-exposure can cause rapid-onset HIT

### Teaching Points
1. HIT is an immune-mediated prothrombotic disorder, NOT a bleeding disorder despite low platelets
2. Antibodies form against PF4-heparin complexes and activate platelets, causing consumption AND thrombosis
3. The 4Ts score helps estimate pre-test probability and guide testing
4. HIT typically occurs 5-10 days after heparin exposure; rapid-onset HIT occurs with recent prior exposure
5. Thrombosis occurs in 30-50% of untreated HIT cases, both venous and arterial
6. Platelet transfusion is contraindicated as it may fuel further thrombosis
7. Warfarin should not be started until platelets recover due to protein C depletion and limb gangrene risk
8. Alternative anticoagulants include argatroban, bivalirudin, and fondaparinux