What are the possible coagulopathies in a patient with epistaxis and hematuria, normal PT and prolonged PTT mixing study?

Coagulopathies in a Patient with Epistaxis, Hematuria, Normal PT, and Prolonged PTT Mixing Study

The most likely diagnosis in a patient with epistaxis, hematuria, normal PT, and prolonged PTT mixing study that doesn't correct is acquired hemophilia A with factor VIII inhibitors, which requires immediate immunosuppressive therapy and bypassing agents for bleeding management. 1

Differential Diagnosis

When evaluating a patient with this clinical presentation, the following coagulopathies should be considered:

1. Acquired Hemophilia A (most likely)

   • Characterized by factor VIII inhibitors
   • Prolonged PTT that doesn't correct on mixing studies
   • Normal PT (factor VII in extrinsic pathway unaffected)
   • Clinical presentation of mucocutaneous bleeding (epistaxis, hematuria)

2. Lupus Anticoagulant

   • Prolonged PTT that doesn't correct with normal plasma
   • Normal PT
   • Paradoxically associated with thrombosis, not bleeding 2

3. Von Willebrand Disease (severe form)

   • Can present with prolonged PTT
   • Mucocutaneous bleeding pattern

4. Heparin Contamination/Therapy

   • Prolonged PTT
   • Normal PT
   • Can be reversed with protamine 3

5. Factor Deficiencies (IX, XI, XII)

   • PTT would typically correct on mixing study

Diagnostic Approach

1. Confirm PTT Prolongation and Mixing Study Results

   • Mixing studies should be performed immediately and after 2-hour incubation to distinguish between factor deficiency and inhibitor presence 1
   • Non-correction suggests presence of an inhibitor

2. Specific Factor Assays

   • Measure factor VIII, IX, XI, XII levels
   • Factor VIII is most commonly affected in acquired hemophilia

3. Bethesda Assay

   • Quantifies inhibitor levels
   • Clinically significant levels are ≥0.6 Bethesda Units (BU)/mL 1

4. Rule Out Medication Effects

   • Check for surreptitious or accidental ingestion of anticoagulants
   • Cases of accidental warfarin ingestion have been reported 4, 5

Management

For Acquired Hemophilia A (most likely diagnosis):

1. Control Acute Bleeding

   • Bypassing Agents:
     • Activated Prothrombin Complex Concentrates (aPCC): 50-100 IU/kg every 8-12 hours (maximum 200 IU/kg/day) 1
     • Recombinant Factor VIIa (rFVIIa): Effective in 86-90% of bleeding episodes within 24 hours 1

2. Immediate Immunosuppressive Therapy

   • First-line regimen:
     • Corticosteroids (prednisone/prednisolone 1 mg/kg/day PO for 4-6 weeks)
     • Consider adding cyclophosphamide (1.5-2 mg/kg/day for up to six weeks) 1
   • Second-line therapy:
     • Rituximab if first-line fails after 4-6 weeks 1

3. Monitoring

   • Monitor aPTT and factor VIII levels monthly for first six months
   • Continue monitoring every 2-3 months up to 12 months 1

For Heparin Contamination/Therapy:

• Protamine administration: 1 mg protamine reverses 100 u heparin 3

For Warfarin Ingestion (if suspected):

• Fresh Frozen Plasma (FFP)
• Vitamin K (5-10 mg IV)
• Prothrombin Complex Concentrate (PCC) for severe cases 3

Common Pitfalls

1. Relying solely on PTT for diagnosis

   • A normal aPTT does not exclude mild hemophilia 1

2. Delayed treatment initiation

   • Immediate immunosuppressive therapy is crucial for acquired hemophilia A 1

3. Inadequate dosing of bypassing agents

   • If inadequate response to first-line bypassing agent after appropriate dosing, switch to the alternative agent 1

4. Using tranexamic acid with aPCC

   • This combination is contraindicated 1

5. Overlooking surreptitious ingestion

   • Consider Munchausen syndrome in healthcare professionals with unexplained coagulopathy 4

Prognosis

With appropriate management including immunosuppressive therapy and bypassing agents, mortality can be reduced from 41% to 20%, significantly improving patient outcomes and quality of life 1. Early diagnosis and prompt treatment are critical to minimize morbidity and mortality.