Pharmacy Program

Delivering Integrated Care and Cost Management

The IHTC works collaboratively with payors to optimize care. We ensure that the patients and families we serve have access to care and therapies, thereby helping to contain costs and reduce both bleeding events and utilization of resources.

The IHTC Pharmacy’s ability to purchase clotting factor through the Public Health Service 340B discount program and our overall pricing structure benefit payors and patients by dispensing clotting factor at significantly reduced prices.

Diagnosis of Thrombosis

Diagnosing deep vein thrombosis (DVT) and pulmonary embolism (PE) may be difficult as the signs and symptoms associated with these disorders are not unique to these conditions. For example, leg pain and swelling or chest pain and shortness of breath may be related to numerous other causes. As a result, objective testing is needed to confirm the diagnosis. Venography and pulmonary angiography remain the gold standards for diagnosis of DVT and PE, respectively, but these tests are now increasingly supplanted by less invasive and less costly procedures. Such noninvasive tests are often incorporated into diagnostic algorithms that are designed to limit the need for more invasive procedures.1

Three types of imaging tests may be used to diagnose venous thrombosis.

Tests using radio labels

Radioactive fibrinogen leg scanning: This test is moderately sensitive and specific for calf and popliteal vein thrombosis, but less sensitive for superficial femoral or ileac vein thrombosis. (see,,zm2346,00.html for graphic)

The AcuTect Venogram: The AcuTect is a synthetic peptide radiopharmaceutial that binds preferentially to the glycoprotein (GP IIa/IIIb receptor) found on activated platelets. The AcuTect venogram is indicated as a test for acute venous thrombosis in the lower extremities of patients with signs and symptoms of acute venous thrombosis. The AcuTect appears to detect acute and not chronic venous thrombosis.

Tests using ultrasound

Doppler-augmented ultrasound and impedance plethysmography (IPG): This test is insensitive to calf vein thrombosis and non-occlusive proximal vein thrombi, although it is sensitive to occlusive proximal thrombi.

Doppler ultrasonography: This is the most widely utilized and available noninvasive test for DVT. It is often used with B-mode imaging of the lower extremities. Doppler ultrasonography has become the dominant test since the 1980’s and has largely replaced impedance plethysmography for noninvasive testing. The positive predictive value of impedance plethysmography is slightly less than that of Doppler ultrasonography.

Tests using X-Rays or Computed Tomography

Venography: This method of testing can detect both calf and proximal vein thrombi.

V/Q scans: Most studies investigating the incidence of pulmonary embolism (PE) in hospitalized patients use lung perfusion scanning as the diagnostic test. V/Q scanning is able to show even small emboli and this ability is enhanced by single photon emission computed tomography (SPECT). Chest films and arterial blood gas studies, however, are essential for proper interpretation of V/Q studies.2 Although the sensitivity of V/Q scanning is sufficiently high, it has low specificity compared to angiography. Both standard angiography and single-slice CT are inadequate to assess the positive predictive value of V/Q scanning. High-resolution CT is promising to correlate the high sensitivity as well as specificity of V/Q scanning, but requires further validation in larger studies. V/Q scanning may be used as a one-step diagnostic approach to PE in patients with a normal chest radiograph. In patients with an abnormal chest radiograph, V/Q scanning should be used in combination with spiral CT. Because the negative predictive value of V/Q scanning for recurrent PE is very high, V/Q scanning tends to be used primarily to exclude rather than confirm PE.3

Helical spiral computed tomography (spiral CT): This technique has a positive predictive value of greater than 95% in clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with a nondiagnostic or high-probability V/Q scan. This is an accurate method for detection and exclusion of PE with the exception of isolated subsegmental PE.

Laboratory testing

The ability of D-dimer assays to exclude the diagnosis of thromboembolic disease is controversial. The accuracy of this test has been shown to correlate with the patient setting. In outpatients, the negative predictive value was 98% (95% confidence interval [CI], 93%-100%) and 99% (94-100%) for the microlatex and ELISA methods, respectively, at the recommended cutoffs. In contrast, in hospitalized patients, the confidence intervals for the areas under the ROC curves included 0.5 (6.0 [95% CI, .50-0.71] and 0.56 [0.44-0.67]). The accuracy of the elevated D-dimer result in the hospitalized patient presumably reflects thrombosis and/or comorbidities other than pulmonary embolism that lead to an increase in D-dimer concentration.4

D-dimer levels may also be predictive of recurrence of VTE after discontinuation of oral anticioagulation. Normal levels obtained one month after discontinuation have a high negative predictive value for recurrence. Additionally, normal D-dimers measured one month after discontinuation of oral anticoagulation have a high negative predictive value for recurrence in subjects with previous unprovoked venous thromboembolism, regardless of whether they are carriers of a form of congenital thrombophilia.5

Special Considerations for Diagnosis of Antiphospholipid Syndrome (APS)

Patients with APS should have at least one clinical and one persistent laboratory finding documented to establish this diagnosis. The APA tests should be positive on at least two occasions greater than 8 weeks apart. In many individuals this diagnosis may occur in the setting of an underlying autoimmune disorder such as systemic lupus erythematosus (SLE), yet can also occur as an isolated entity meaning in the absence of an underlying systemic disease. This latter group of patients is referred to as having primary antiphospholipid-protein syndrome (PAPS). In some patients, PAPS may progress to SLE over time. APS may also be induced by drugs or an underlying malignancy.

Special Considerations for Diagnosis of Heparin-Induced Thrombocytopenia (HIT)

The diagnosis of suspected HIT should be based on a clinical assessment made by a medical care provider experienced with this condition, in conjunction with a variety of specialized laboratory tests. Laboratory assays for diagnosing HIT are described here. [link to Laboratory Diagnosis of HIT in Thrombosis_Acquired Causes_Provider_FINAL_SEP2010.doc ] If HIT is confirmed, all forms of heparin must be stopped. This includes the removal of heparin-coated catheters and the discontinuation of all heparin flushes of catheters.


  1. Weitz JI. Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism. Presentation at the Surgeon General Workshop on Deep Vein Thrombosis. 2006. Available at: . Accessed March 10, 2010.
  2. Niethammer JG 3rd, et al. Pulmonary embolism. How V/Q scanning helps in diagnosis. Postgrad Med. 1990 Jan;87(1):263-7, 270.
  3. Schümichen C. V/Q-scanning/SPECT for the diagnosis of pulmonary embolism. Respiration. 2003;70:329-342.
  4. Schrecengost J, et al. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem. 2003;49:1483-1490.
  5. Palareti G, et al. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia. Circulation. 2003;108:313-318.
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