Hypoprothrombinemia Workup

Updated: Jan 15, 2019
  • Author: J Nathan Hagstrom, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
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Workup

Laboratory Studies

Hypoprothrombinemia is determined by performing a specific assay for factor II activity.

The prothrombin time (PT), usually indicated as an international normalized ratio (INR), and the activated partial thromboplastin time (aPTT) are elevated in hypoprothrombinemia. However, both the PT and the aPTT can be elevated in numerous single-factor and multiple-factor deficiencies; therefore, their elevation is not specific for hypoprothrombinemia.

First, determine if the prothrombin deficiency is isolated or associated with other factor deficiencies. Determine this status by performing assays for factors VII, IX, and X, which are the other vitamin K–dependent procoagulants.

Performing assays for factor V and VIII activity may also be helpful. Factor V activity is decreased in liver disease and DIC. Factor VIII activity is decreased in disseminated intravascular coagulation (DIC) but not often in liver disease.

If other vitamin K–dependent factors are decreased, rule out vitamin K deficiency, liver disease, or both. Vitamin K and vitamin K epoxide levels can be determined by select clinical laboratories. Warfarin levels can also be directly measured by some commercial clinical laboratories.

If multiple-factor deficiencies include factors other than vitamin K–dependent factors, evaluate the patient for DIC, liver disease, or both.

If isolated factor II deficiency is present, test for an inhibitor by performing a mixing study. In the presence of an inhibitor, the PT is not corrected when the patient's plasma is mixed 1:1 with normal pooled plasma. If an inhibitor is detected, suspect a lupus anticoagulant, which can be detected by using the dilute Russell viper venom test (DRVVT) or the tissue thromboplastin inhibition test. Anticardiolipin antibodies are found in about 60-70% of patients with a lupus anticoagulant. The presence of these antibodies helps to confirm the diagnosis of an antiphospholipid antibody syndrome as well.

In cases of suspected inherited prothrombin deficiency, assessment of factor II activity in family members may be helpful. Numerous research laboratories across the United States can perform tests for factor II antigen levels and screen for mutations in the prothrombin gene.

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Imaging Studies

Neonates found to have a severe inherited bleeding diathesis should undergo head CT scanning to evaluate for intracranial hemorrhage, regardless of their symptoms or signs.

Head ultrasonography may be used but is not as sensitive as CT scanning.

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Other Tests

The bleeding time is not a useful test for evaluating hypoprothrombinemia. The bleeding time may or may not be elevated. Although it is certainly elevated in severe platelet function disorders, the degree of elevation is not predictive of bleeding risk, and its sensitivity for milder forms of platelet dysfunction is poor.

Other means of testing platelet function, such as platelet function assay (PFA) or platelet aggregation testing, are also not helpful in evaluating hypoprothrombinemia. Their use in screening for platelet function disorders has not been fully defined.

Thromboelastography and thrombin generation testing is abnormal in hypoprothrombinemia.

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