High Molecular Weight Kininogen (HMWK / Fitzgerald Factor)

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Turnaround Time: 4 - 8 days
CPT Code:


Test Type: 2 mL Plasma, frozen
Stability Time:

Freeze; four freeze/thaw cycles are acceptable. Stable at room temperature for four hours.


Useful in the evaluation of an elevated APTT. Measurement of high molecular weight kinonogen concentration.

High molecular weight kininogen (HMWK) is a 110 kilodalton single-chain nonenzymatic cofactor synthesized in the liver which is central to contact activation reactions.6 It forms a complex with prekallikrein and factor XI. HMWK's plasma concentration is 70 mg/mL and its plasma half-life is approximately 144 hours. Factors VIII, IX, XI, XII, prekallikrein, and HMWK are the coagulation factors of the intrinsic coagulation pathway. Factor XII, high molecular weight kininogen, and prekallikrein are also called the “contact” factors. Factor XI is sometimes included in this designate of “contact” factors because of its interaction with others listed. Factor XI is activated by factor XIIa formed through activation of XII by HMWK-prekallikrein complex on endothelial cells. HMWK proteolysis leads to the production of bradykinin, a mediator of vasodilation, smooth muscle contractions, and increased vascular permeability. Other functions of HMWK include inhibition of thrombin-induced platelet aggregation, participant in fibrinolysis, as well as having surface-binding antiadhesive properties. Contact factor deficiencies have no hemorrhagic consequence; however, the contact factors are necessary for normal aPTT clot formation in the laboratory. Deficiency of HMWK produces markedly prolongs aPTT results. Hereditary HMWK deficiency conditions are inherited through an autosomal recessive pattern. Although the aPTT is prolonged in deficiencies of factor XII, prekallikrein, and high molecular weight kininogen, there is generally no clinical evidence of bleeding unless other contributing factors are present. These deficiencies are generally diagnosed when evaluating a prolonged aPTT with no other explanation (ie, other screening tests) and clinical history is negative for a bleeding disorder.

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. PubMed 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. PubMed 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. PubMed 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. PubMed 10539100

6. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook.
Aurora, Colo: Esoterix−Colorado Coagulation; 2006.

Collection Details:

Collection Instructions:

Blue-top (sodium citrate) tube.

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 and carefully remove the plasma using a plastic transfer pipette, being careful not to disturb the cells. 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.

Freeze; four freeze/thaw cycles are acceptable. Stable at room temperature for four hours.