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Home > Coagulation > Abnormal PT and PTT - causes

Coagulation
Coagulation laboratory tests
Abnormal PT and PTT - causes

Authors: Tori Seasor, M.D., Karen A. Moser, M.D.

Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.

Last author update: 1 December 2020

Last staff update: 21 May 2021

Copyright: 2002-2022, PathologyOutlines.com, Inc.

PubMed Search: Abnormal PT and PTT - causes

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Table of Contents
Definition / general | Essential features | Terminology |
Pathophysiology | Clinical features | Symptoms |
Laboratory | Differential diagnosis | Board review style
question #1 | Board review style answer #1 | Board
review style question #2 | Board review style answer #2

Cite this page: Seasor T, Moser KA. Abnormal PT and PTT

- causes. PathologyOutlines.com website. https://www.pathol
ogyoutlines.com/topic/coagulationabnormalPTPTT.html. Acc
essed September 3rd, 2022.

Definition / general
Prothrombin time (PT) and activated partial thromboplastin
time (aPTT) are common initial tests in the evaluation of
patients with suspected bleeding disorders
PT evaluates extrinsic and common pathways
aPTT measures intrinsic and common pathways

Essential features
PT and aPTT methods measure time to fibrin clot
formation
PT and aPTT results are reported in seconds
Common causes of prolonged PT or aPTT are factor
deficiencies, inhibitors (specific or nonspecific), liver
failure, disseminated intravascular coagulation (DIC),
anticoagulants and preanalytic factors
Prolonged PT and aPTT can be further evaluated with
mixing studies or other coagulation tests (such as factor
activities and lupus anticoagulant testing) if indicated

Terminology
Prolonged PT or aPTT
Abnormal coagulation screening tests
Abnormal clotting time

Pathophysiology

Images hosted on other servers:

Schematic of
coagulation
cascade

Clotting time Key differential diagnoses

prolonged

Factor deficiency or inhibitor (VII, X, V,

II)
Prothrombin Warfarin
time (PT) Vitamin K deficiency
Liver disease
Direct Xa inhibitor

Factor deficiency or inhibitor (VIII, IX,

XI, contact factors)
Activated
Rarely, von Willebrand disease (if VIII
partial
is low enough to prolong aPTT)
thromboplastin
Heparin
time (aPTT)
Direct thrombin inhibitor
Lupus anticoagulant

Common pathway factor deficiency or

inhibitor (X, V, II)
Warfarin (high doses) or superwarfarin
Vitamin K deficiency
Disseminated intravascular
PT and aPTT coagulation
Liver disease
Direct thrombin inhibitors
Direct Xa inhibitors
Lupus anticoagulant (rarely)
Heparin (very high doses)

PT evaluates clotting within the extrinsic and common

coagulation pathways
Causes of isolated prolonged PT (Clin Lab Med 2009;29:253,
Lab Med 2017;48:295)
Deficiency of or inhibitor to factor VII
Mild decrease in common pathway factor(s)
Medications: warfarin and other vitamin K antagonists,
direct Xa inhibitors
Liver disease (early / mild)
DIC (early)
Vitamin K deficiency
aPTT evaluates clotting within the intrinsic and common
coagulation pathways
Causes of isolated prolonged aPTT (Lab Med 2017;48:295,
Semin Thromb Hemost 2014;40:195, Am J Hematol
2013;88:82):
Deficiency of or inhibitor to factors VIII, IX, or XI
Deficiency of contact factors (factor XII, prekallikrein,
high molecular weight kininogen)
Contact factor deficiency is not associated with
clinical bleeding
Isolated aPTT prolongation rarely occurs with multiple
factor deficiencies such as DIC or liver failure
Lupus anticoagulant (nonspecific inhibitor)
Medications: unfractionated heparin (note: aPTT is
commonly used to monitor unfractionated heparin
therapy), direct thrombin inhibitors
Causes of prolonged PT and aPTT
Deficiency of or inhibitor to common pathway factors
Dilutional coagulopathy
DIC
Nonspecific inhibitor: lupus anticoagulant with
hypoprothrombinemia
Afibrinogenemia, hypofibrinogenemia or
dysfibrinogenemia
Severe liver disease
Vitamin K deficiency (severe)
Medications: supratherapeutic warfarin, superwarfarins,
supratherapeutic unfractionated heparin, direct Xa
inhibitors (high levels), direct thrombin inhibitors (high
levels)
Prolonged PT or aPTT can prompt further evaluation with
a mixing study or factor assays if factor deficiency or
inhibitor suspected (Lab Med 2017;48:295, Mayo Clin Proc
2007;82:864)
A mixing study is nonspecific but patterns may support
either a factor deficiency or a factor inhibitor

Clinical features
Conditions associated with prolonged PT or aPTT: (Lab
Med 2017;48:295, Mayo Clin Proc 2007;82:864, Clin Lab Med
2009;29:253, Am J Hematol 2013;88:82)
Factor deficiency:
Decreased factor activity with one or more factor
assays
Includes hemophilia (deficiency of factor VIII, IX or
XI)
Bleeding
Specific factor inhibitor:
Decreased factor activity and positive Bethesda
(inhibitor) assay for a specific factor
Bleeding
Nonspecific inhibitor (e.g. lupus anticoagulant):
Positive lupus anticoagulant testing (e.g. dRVVT,
hexagonal phospholipid neutralization assay, platelet
neutralization procedure)
No specific factor inhibitor detected with Bethesda
assay
May have thrombosis or be asymptomatic
Vitamin K deficiency:
Decreased activity of factors II, VII, IX, X
May have bleeding or be asymptomatic
Anticoagulant medications:
Heparin - prolonged aPTT and prolonged TT that
correct with heparin neutralization, normal reptilase
time
Warfarin - decreased activity of factors II, VII, IX, X
Direct thrombin inhibitors - prolonged aPTT and
prolonged TT that do not correct with heparin
neutralization, normal reptilase time
Direct Xa inhibitors - abnormal anti-Xa activity assay
Disseminated intravascular coagulation (DIC):
Decreased activity of multiple factors, including
fibrinogen; markedly elevated D-dimer
May have bleeding and / or thrombosis
Liver failure:
Decreased activity of all coagulation factors except
for factor VIII which is not produced by hepatocytes
Factor V activity is decreased in liver failure but not
with vitamin K antagonists or vitamin K deficiency
May have bleeding or be asymptomatic
Dysfibrinogenemia, hypofibrinogenemia,
afibrinogenemia:
Dysfibrinogenemia - fibrinogen activity decreased to
a greater degree than fibrinogen antigen
Hypofibrinogenemia / afibrinogenemia - fibrinogen
activity and antigen decreased to a similar degree
Bleeding

Symptoms
Abnormal PT / aPTT can be asymptomatic or associated
with bleeding or clotting, depending on the underlying
cause

Laboratory
PT / aPTT testing are clotting times (Lab Med 2017;48:295)
Current coagulation analyzers use 1 of 2 strategies for
clot detection
Electromechanical
Optical
Sample for testing: platelet poor plasma in 3.2% sodium
citrate
PT: thromboplastin (tissue factor combined with
phospholipid) and calcium chloride are added to the
sample to initiate clotting
aPTT: a contact factor activator (e.g. kaolin, silica)
combined with phospholipid and calcium chloride are
added to the sample to initiate clotting
Reagents used for PT and aPTT testing vary between labs
and show different factor sensitivities as well as different
sensitivity to lupus anticoagulants and anticoagulant
medications
Each laboratory must understand the performance
characteristics of the reagent it uses
PT and aPTT results are reported in seconds

Differential diagnosis
Preanalytic variables that may falsely prolong PT and
aPTT (Lab Med 2017;48:295, Mayo Clin Proc 2007;82:864)
Sample drawn in EDTA instead of citrate
EDTA strongly chelates calcium, falsely prolonging PT
and aPTT, among other abnormalities (Lab Med
2012;43:1)
Delay in specimen processing
Loss of labile factors (V, VIII) may falsely prolong PT
and aPTT
Underfilling blood collection tube
Causes relative citrate excess and false prolongation of
PT and aPTT
High hematocrit
Increased RBC and decreased plasma in tube causes
relative citrate excess and false prolongation of PT and
aPTT

Board review style question #1

Which of the following is the most likely possible cause of
combined PT and aPTT prolongation?

A. Factor VII deficiency

B. Low hematocrit
C. Lupus anticoagulant
D. Underfilled collection tube

Board review style answer #1

D. Underfilled collection tube. Underfilling the blood
collection tube will result in a prolongation of aPTT and PT
due to the increased concentration of citrate. High
hematocrit (not low hematocrit) can also result in a relative
excess of citrate due to increased red blood cells and a
relatively smaller volume of plasma in the tube. Lupus
anticoagulant affects aPTT to a greater degree than PT due
to the high concentration of phospholipids in PT reagents.
Factor VII deficiency would be expected to prolong the PT
but not the aPTT.

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Reference: Abnormal PT and PTT - causes

Board review style question #2

A 68 year old man has an aPTT of > 150 s (reference
interval 24 - 35 s) and PT of 12 s (reference interval 12 -
15.5 s). A 1:1 aPTT mixing study result is 33 s. He has no
personal or family history of a bleeding disorder. What is the
most likely cause of his aPTT prolongation?

A. Factor IX deficiency
B. Factor XIII deficiency
C. Prekallikrein deficiency
D. Von Willebrand factor deficiency

Board review style answer #2

C. Prekallikrein deficiency. Prekallikrein deficiency causes
prolonged aPTT that corrects in a 1:1 mixing study and is not
associated with clinical bleeding. The other contact factors
(factor XII and high molecular weight kininogen) give a
similar picture. Factor IX deficiency can also cause a
prolonged aPTT that corrects in a mixing study but it is
associated with a bleeding diathesis (hemophilia B). Factor
XIII deficiency does not prolong the PT or aPTT (recall that
factor XIII crosslinks fibrin but the PT and aPTT reaction
endpoint is the formation of fibrin and these tests do not
measure the effect of factor XIII). Some types of von
Willebrand disease may be associated with prolonged aPTT
(e.g. type 2N, type 3) due to significantly decreased factor
VIII activity but the degree of aPTT prolongation is typically
less than was seen in the case in this question.

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Reference: Abnormal PT and PTT - causes

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