What is the cause of elevated Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)?

Causes of Elevated PT and PTT

Disseminated Intravascular Coagulation (DIC) is the most common and serious cause of simultaneously elevated PT and PTT, requiring prompt identification and treatment of the underlying condition to reduce mortality. 1

Common Causes of Elevated PT and PTT

1. Consumptive Coagulopathies

• Disseminated Intravascular Coagulation (DIC)
  • Characterized by systemic activation of coagulation leading to consumption of clotting factors
  • Diagnostic criteria: platelet count <50 × 10^9/L, PT >14 seconds, fibrinogen <1.5 g/L, elevated D-dimer >0.5 mg/L 1
  • Rapid changes in coagulation parameters are hallmark of DIC 2
  • Often triggered by sepsis, trauma, malignancy, or obstetric complications

2. Medication-Related Causes

• Anticoagulant Therapy
  • Warfarin primarily affects PT/INR 3
  • Heparin primarily affects PTT
  • Direct oral anticoagulants can affect both tests
  • Monitoring intervals should be based on patient response and medication stability 3

3. Liver Disease

• Cirrhotic Coagulopathy
  • Reduced synthesis of clotting factors II, V, VII, IX, X
  • PT typically more affected than PTT
  • Distinguished from DIC by stable parameters that don't change rapidly 2
  • May have normal or elevated fibrinogen (as acute phase reactant) 2

4. Vitamin K Deficiency

• Causes include:
  • Malnutrition
  • Malabsorption syndromes
  • Prolonged antibiotic therapy
  • Biliary obstruction
  • Treatment: Vitamin K 2.5-10 mg (up to 25 mg in severe cases) 4

5. Acquired Factor Inhibitors

• Acquired Hemophilia A
  • Autoantibodies against Factor VIII
  • Typically presents with isolated PTT elevation, but can affect both in severe cases
  • Mixing studies show failure to correct after 1-2 hours incubation 2

6. COVID-19 Coagulopathy

• COVID-19 infection
  • Can cause coagulopathy with elevated PT/PTT
  • PT ratio and PTT ratio ≥1.5 considered significant 2
  • Associated with increased mortality when severely abnormal 2

Diagnostic Approach

1. Assess for bleeding or thrombosis

   • Clinical bleeding suggests consumptive process or factor deficiency
   • Thrombosis may indicate DIC or antiphospholipid syndrome

2. Laboratory evaluation:

   • Complete PT/PTT panel with specific factor assays
   • Fibrinogen level (decreased in DIC, normal/increased in liver disease)
   • D-dimer (markedly elevated in DIC)
   • Mixing studies to distinguish factor deficiency from inhibitors 2
   • Factor VIII and von Willebrand factor levels (low in consumptive processes) 2

3. Interpret PT/PTT ratios:

   • PT/PTT ratio ≥1.5 times normal indicates significant coagulopathy 2, 1
   • Consider reagent variability - different laboratory tests have different sensitivities 5

Management Principles

1. Treat the underlying cause

   • Most important step in managing coagulopathy 1

2. Blood product support

   • Fresh frozen plasma (15 ml/kg) for significant bleeding or before invasive procedures 2
   • Consider fibrinogen replacement with cryoprecipitate if fibrinogen <1 g/L 2
   • Platelet transfusion for counts <50 × 10^9/L with active bleeding 1

3. Vitamin K administration

   • For vitamin K deficiency or warfarin reversal: 2.5-10 mg (up to 25 mg in severe cases) 4

Important Pitfalls to Avoid

1. Misinterpreting normal coagulation screens

   • Normal PT/PTT does not exclude coagulopathy, especially in early or subclinical forms 1

2. Overlooking pre-analytical variables

   • Improper sample collection (underfilled tubes, prolonged tourniquet time)
   • Delayed sample processing
   • Heparin contamination from IV lines

3. Relying solely on INR for non-warfarin patients

   • INR was designed specifically for warfarin monitoring and may be misleading in other contexts 2

4. Ignoring clinical context

   • Laboratory abnormalities may not correlate with clinical bleeding risk 6
   • Prolonged PT in pediatric leukemia patients often doesn't correlate with bleeding symptoms 6

5. Failing to recognize PTT confounding

   • Lupus anticoagulant and other inhibitors can artificially prolong PTT 7
   • May lead to inappropriate anticoagulant dosing 7

By systematically evaluating the potential causes of elevated PT and PTT while considering the clinical context, clinicians can identify the underlying etiology and implement appropriate management strategies to reduce morbidity and mortality.