Table of Contents

PT/aPTT abnormalities

Causes

Test result Causes of test result pattern
PT aPTT
Prolonged Normal Inherited
Factor VII deficiency
Acquired
Mild vitamin K deficiency
Liver disease
Warfarin
DIC
Normal Prolonged Inherited
Deficiency of factor VIII, IX, or XI
Deficiency of factor XII, prekallikrein, or HMW kininogen (not associated with a bleeding diathesis)
von Willebrand disease (variable)
Acquired
Heparin, dabigatran, argatroban, direct factor Xa inhibitors (variable)
Acquired inhibitor of factor VIII, IX, XI, or XII
Acquired von Willebrand syndrome
Lupus anticoagulant (more likely to be associated with thrombosis than bleeding)
Prolonged Prolonged Inherited
Deficiency of prothrombin, fibrinogen, factor V, or factor X
Combined factor deficiencies
Acquired
Liver disease
DIC
Severe vitamin K deficiency
Anticoagulants (supratherapeutic doses of many anticoagulants, combined heparin and warfarin, direct thrombin inhibitors, anticoagulant rodenticide poisoning)*
Acquired inhibitor of prothrombin, fibrinogen, factor V, or factor X
Amyloidosis-associated factor X deficiency

Anticoagulants

Drug class Drug Brand name(s) PT aPTT Anti-factor Xa activity
Vitamin K antagonists Warfarin Jantoven ↑ ↑/– * –
Acenocoumarol Sintrom ↑ ↑/–* –
Heparins Unfractionated heparin – ↑ ↑
LMW heparins
Enoxaparin
Dalteparin
Nadroparin
Lovenox
Fragmin
Fraxiparine 		– ↑/– ↑
Fondaparinux Arixtra – ↑/– ↑
Direct thrombin inhibitors Argatroban Acova ↑ ↑ –
Dabigatran Pradaxa ↑/– ↑ –
Direct factor Xa inhibitors Rivaroxaban Xarelto ↑/– ↑/– ↑Δ
Apixaban Eliquis ↑/– ↑/– ↑Δ
Edoxaban Lixiana, Savaysa ↑Δ

* Warfarin has a weak effect on most aPTT reagents. However, warfarin use will increase the sensitivity of the aPTT to heparin effect.

¶ While heparin, LMW heparin, and fondaparinux should, in theory, prolong the PT as indirect thrombin inhibitors, in practice most PT reagents contain heparin-binding chemicals that block any heparin effect below a concentration of 1 unit/mL. Above concentrations of 1 unit/mL, heparin effect on the PT may be observed.

Δ Anti-factor Xa activity testing must be calibrated for the specific anticoagulant; this information should be verified with the clinical laboratory.

In principle, many anticoagulants affect common pathway factors and can prolong both the PT and the aPTT if present at high enough levels. As examples:

  1. Warfarin typically prolongs the PT alone, but at high levels warfarin can prolong both tests.
  2. Heparin typically prolongs the aPTT alone (because PT reagents contain heparin-binding agents that block heparin effect), but at high levels heparin can prolong both tests.
  3. Direct thrombin inhibitors (argatroban, dabigatran) typically prolong both tests, but at low levels dabigatran may not prolong the PT.
  4. Direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) can prolong the PT and aPTT, although these effects are variable.

Thrombophilia Testing

Thrombophilic disorder Clinical settings and anticoagulants
Acute thrombosis Heparin therapy Warfarin Direct oral anticoagulants
Factor V Leiden Unchanged Unchanged Unchanged Unchanged
Prothrombin G20210A Unchanged Unchanged Unchanged Unchanged
Protein C (PC) deficiency Unchanged Unchanged Cannot measure Cannot measure using functional assays
Protein S (PS) deficiency Can be lowered Unchanged Cannot measure Cannot measure using functional assays
Antithrombin (AT) deficiency Can be lowered Lowered Unchanged Cannot measure using functional assays
Antiphospholipid antibodies Unchanged Unchanged Unchanged Unchanged
Lupus anticoagulant Unchanged Cannot measure False positives possible Cannot measure
Increased factor VIII activity Acute phase reactant. Do not test while inflammation is still present.
Acquired AT deficiency
Neonatal period; pregnancy; liver disease; DIC; nephrotic syndrome; major surgery; acute thrombosis; treatment with L-asparaginase, heparin, or estrogens
Acquired protein C deficiency
Neonatal period; liver disease; vitamin K deficiency; DIC, chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil; inflammation; treatment with warfarin or L-asparaginase
Acquired protein S deficiency
Neonatal period; pregnancy; liver disease; vitamin K deficiency; DIC; treatment with warfarin, L-asparaginase, or estrogens

Hepatic Synthesis