PT/aPTT abnormalities

Causes

Test result		Causes of test result pattern
PT	aPTT	Causes of test result pattern
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	↑	↑/– *	–
Vitamin K antagonists	Acenocoumarol	Sintrom	↑	↑/–^*	–
Heparins	Unfractionated heparin		–^¶	↑	↑
	LMW heparins Enoxaparin Dalteparin Nadroparin	Lovenox Fragmin Fraxiparine	–	↑/–	↑
	Fondaparinux	Arixtra	–	↑/–	↑
Direct thrombin inhibitors	Argatroban	Acova	↑	↑	–
Direct thrombin inhibitors	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:

Warfarin typically prolongs the PT alone, but at high levels warfarin can prolong both tests.
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.
Direct thrombin inhibitors (argatroban, dabigatran) typically prolong both tests, but at low levels dabigatran may not prolong the PT.
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
Thrombophilic disorder	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

Factor I (fibrinogen)
Factor II (prothrombin)
Factor V
Factor VII
Factor IX
Factor X
Factor XII
Factor XIII

USC IM

Table of Contents

PT/aPTT abnormalities

Causes

Anticoagulants

Thrombophilia Testing

Hepatic Synthesis