Definition

Precise PT/PTT values depend on your lab’s upper limit of normal. It is important to remember that patients may have more than one etiology of coagulopathy, and to look back at previous values to see how far they are from their baseline.

Differential Diagnosis

• Isolated prolonged PT: warfarin, liver disease, vitamin K deficiency (antibiotics, poor nutrition, malabsorption), deficiency in or inhibitor to factor VII, DIC.
• Isolated prolonged PTT: heparin, direct thrombin inhibitor, congenital deficiency of VIII, IX, XI, XII, prekallikrein, or high-molecular weight kininogen, factor VIII inhibitor, von Willebrand’s disease, anti-phospholipid antibody, advanced liver disease, DIC.
• Prolonged PT and PTT: excessive warfarin anticoagulation, direct thrombin inhibitor, DIC, advanced liver disease, severe vitamin K deficiency, factor X, V, or prothrombin deficiency, factor V and prothrombin autoantibodies, hypofibrinogenemia or dysfibrinogenemia.

Evaluation

• Depending on the precise clinical picture, evaluation may be focused on the suspected etiology.
• If no etiology is favored, start with LFTs to assess liver function, a peripheral smear and fibrinogen for evidence of DIC, and a review of medications.
• For unexplained prolonged PT and/or PTT, mixing studies may also be helpful to distinguish between deficiency vs. inhibitor.

Management

• Use oral vitamin K to correct mild to moderate PT prolongation. Correction occurs within 10-12 hours.
• For elevated INR with warfarin use, see section Warfarin for further details.
• Activated prothrombin complex (FEIBA®) and recombinant activated factor 7 (Novoseven®) have been used in patients with factor 8 or 9 inhibitors or factor 7 deficiency. Off label use has involved patients with severe coagulopathy and bleeding refractory to standard corrective measures (e.g., trauma) but runs a serious risk of thrombotic events. Seek a Hematology and pharmacy consult for dosing and assessment of your patient’s candidacy for these costlier options.
• For heparin associated bleeding:
  • Unfractionated heparin: protamine 1 mg for every 100 units of heparin given. Dose by adding the amount given during each prior hour divided by 2# (# = number of hours since hep gtt started).
    • For example, a patient on a heparin drip at 500 units/hour for 3 hours (without a bolus) would have approximately (500/20)+(500/21)+(500/22) = 875 units of circulating heparin. Therefore, the patient should be given 8-9 mg of protamine.
  • Enoxaparin: 1 mg protamine per 1 mg enoxaparin given. Protamine may reverse 40-50% of the drug effect.

Levi M, Levy MH, Anderson HF and Truloff D. Safety of activated factor VII in randomized clinical trials.  N Engl J Med 2010;363:1791-800.