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Coagulation

Coagulation laboratory tests

aPTT - Activated partial thromboplastin time


Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update November 2012
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.

General
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● Also called partial thromboplastin time (PTT); originally described in 1953 (J Lab Clin Med 1953;41:637)
● Second most commonly performed coagulation test (after PT)
● Measures clotting time from factor XII activation through fibrin formation (i.e. intrinsic and common pathway); more sensitive to intrinsic factor deficiencies
● Used to monitor heparin or direct thrombin inhibitors such as hirudin

Methodology
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● 3.2% citrate tube is recommended; use of 3.8% citrate as anticoagulant causes prolonged PTT if samples are < 90% filled compared to 100% filled (no difference in result with 3.2% citrate between filled volumes of 60% and 100%)
● Can assay heparinized samples up to 4 hours after phlebotomy if centrifuged within 1 hour of collection; have shorter PTT if stored uncentrifuged at room temperature (up to 50% decrease at 4 hours), due to release of PF4 from platelets, which neutralizes heparin
● Mix patient plasma with excess calcium (to counteract the citrate anticoagulant), phospholipid (called partial thromboplastin since tissue factor is not present) and intrinsic pathway activator such as silica, kaolin, celite or elagic acid
● After drawing, invert gently to mix

Interpretation
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● Target ratio is 1.5 to 3.0 (compared to nonheparinized samples); abnormal values may cause bleeding, thrombosis, morbidity or death
● Markedly prolonged values may be due to long acting warfarin-like rodenticide toxicity (Arch Pathol Lab Med 2004;128:e181)
● Values are normally higher in newborns (up to 55 seconds), decrease to adult levels at age 6 months; values are smaller with acute phase reactions, which elevate Factor VIII levels
● INR differs with 3.8 vs. 3.2% citrate (Arch Pathol Lab Med 1997;121:956)

Quality control
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● Therapeutic range for heparin should be determined specific to each laboratory’s reagent and instrument system, and redetermined if method changes; determine by comparing ex vivo specimens, preferably with an appropriated validated heparin assay or with a previously calibrated PTT specimen, using a method to control for reagent drift; determine equivalence using ex vivo plasma samples obtained from patients treated with unfractionated heparin, not spiked in vitro heparinized plasma samples

Algorithms for working up a prolonged PTT:
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● Add heparinase; if PTT corrects to normal, prolongation is due to presence of heparin
● Mixing study (determine if etiology is factor deficiency or factor inhibitor); mix patient plasma with equal amount of normal plasma and determine the PTT of the mixture after incubation for 2 hours
     ● If PTT of mixture is normal, prolonged PTT is likely due to factor deficiency; do assays for factors VIII, IX, XI and XII; if PT is also prolonged, consider common pathway factor assays also
     ● If PTT of mixture is still prolonged, suggests presence of inhibitor, usually lupus coagulant; perform lupus coagulant assay; also possible if heparin is present (should have tested for in first step above) or rare factor inhibitors
     ● If PTT of mixture is initially normal but becomes prolonged after incubation for 1-2 hours, may be due to factor VIII inhibitor; perform factor VIII assay - if decreased, perform assay for factor VIII inhibitor

End of Coagulation > Coagulation laboratory tests > aPTT - Activated partial thromboplastin time


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