Heparin Cofactor II

CPT: 85130
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Test Details


  • Dermatan Sulfate Cofactor
  • HCII
  • Heparin Cofactor A


Assessment of thrombotic risk associated with heparin cofactor II levels


This procedure may be considered by Medicare and other carriers as investigational and, therefore, may not be payable as a covered benefit for patients.


Patient plasma is incubated with excess thrombin in the presence of dermatan sulfate. Residual thrombin activity reacts with chromogenic substrate and the color intensity is inversely proportional to heparin cofactor II levels. Heparin levels up to 1 unit/mL do no affect the heparin cofactor II assay.

Reference Interval

In healthy adults, heparin cofactor II reference range in plasma is 65% to 165%. Plasma levels of heparin cofactor II are approximately 50% of adult levels at birth and reach adult levels at six months of age.

Additional Information

Heparin cofactor II is a glycoprotein that belongs to the serine protease inhibitor family.6 Heparin cofactor II, also known as heparin cofactor A or dermatan sulfate cofactor, has a molecular weight of approximately 65 kilodaltons and has a plasma concentration of 9 mg/dL. Heparin cofactor II is synthesized by the liver and has a plasma half-life of 60 hours. Heparin cofactor II specifically inhibits thrombin, in contrast to antithrombin, which inhibits thrombin, factor Xa, and other serine proteases. The inhibition of thrombin by heparin cofactor II is approximately 10 times slower than antithrombin-mediated inhibition and occurs through the formation of equimolar complexes between the reactive site of the inhibitor and the active site of thrombin. The antithrombotic activity of heparin cofactor II is greatly enhanced (over 1000-fold) in the presence of heparin and dermatan sulfate. The physiologic function of the molecule is unclear, but its role may be to serve as an antithrombotic agent in the presence of dermatan sulfate. Acquired deficiencies of heparin cofactor II are reported in patients with liver disease and disseminated intravascular coagulation. Conversely, increased levels of heparin cofactor II may be observed in individuals with renal disorders with proteinuria, during pregnancy, and with oral contraceptive usage. Inherited deficiency of heparin cofactor II has been reported in rare instances and is inherited as an autosomal dominant trait. A clear relationship between increased risk of thrombosis and heparin cofactor II deficiency has not been established since deficiency of heparin cofactor II is observed in both healthy individuals and those with thrombotic episodes. Limited studies have shown that heterozygosity for heparin cofactor II is not a likely risk for thrombosis without other concomitant risk factors. Other studies have reported thrombotic episodes in 36% of individuals with the deficiency.

Specimen Requirements


Plasma, frozen


2 mL

Minimum Volume

1 mL


Blue-top (sodium citrate) tube

Patient Preparation

Do not draw from an arm with a heparin lock or heparinized catheter.


Citrated plasma samples should be collected by double centrifugation. Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.1 Evacuated collection tubes must be filled to completion to ensure a proper blood to anticoagulant ratio.2,3 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples, except when using a winged blood collection device (ie, "butterfly"), in which case a discard tube should be used.4,5 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternate anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes. Centrifuge for 10 minutes and carefully remove 2/3 of the plasma using a plastic transfer pipette, being careful not to disturb the cells. Deliver to a plastic transport tube, cap, and recentrifuge for 10 minutes. Use a second plastic pipette to remove the plasma, staying clear of the platelets at the bottom of the tube. Transfer the plasma into a LabCorp PP transpak frozen purple tube with screw cap (LabCorp N° 49482). Freeze immediately and maintain frozen until tested. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.

Storage Instructions

Freeze. Stable refrigerated for 48 hours.

Clinical Information


1. Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin Pathol. 1997 Jan; 107(1):105-110. 8980376
2. Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant. Am J Clin Pathol. 1998 Jun; 109(6):754-757. 9620035
3. National Committee for Clinical Laboratory Standardization. Collection, Transport, and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline. 5th ed. Villanova, Pa: NCCLS; 2008. Document H21-A5:28(5).
4. Gottfried EL, Adachi MM. Prothrombin time and activated partial thromboplastin time can be performed on the first tube. Am J Clin Pathol. 1997 Jun; 107(6):681-683. 9169665
5. McGlasson DL, More L, Best HA, Norris WL, Doe RH, Ray H. Drawing specimens for coagulation testing: Is a second tube necessary? Clin Lab Sci. 1999 May-Jun; 12(3):137-139. 10539100
6. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook. Aurora, Colo: Esoterix−Colorado Coagulation; 2006.


Church FC, Shirk RA, Phillips JE. Heparin cofactor II. In: High KA, Roberts HR, eds. Molecular Basis of Thrombosis and Hemostasis. New York, NY: Marcel Dekker;1995:379-392.
Goodnight SH, Hathaway WE. Disorders of Hemostasis and Thrombosis: A Clinical Guide. 2nd ed. New York, NY: McGraw-Hill; 2001.
Lane DA, Boisclair MD. The serpin inhibitors of blood coagulation: Antithrombin and heparin cofactor II. In: Thomson JM, ed. Blood Coagulation and Haemostasis. New York, NY: Churchill Livingstone;1991:45-70.


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
500187 Heparin Cofactor II 500189 Heparin Cofactor II** % 3268-0

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