External validation of the HIT Expert Probability (HEP) score.

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.

Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review.

Venous thromboembolic events (VTEs) represent a serious complication related to hormonal contraception and hormone replacement therapy (HRT). Evidence on hormonal contraceptive- and HRT-related VTEs is derived almost exclusively from observational studies and points to a 2- to 6-fold increased relative risk of VTEs with either therapy. Oral contraceptive pills that contain third-generation progestins (desogestrel or gestodene) seem to be associated with greater VTE risk than those that contain levonorgestrel. Oral contraceptive pill use and HRT are associated with exponentially higher VTE relative risks when used by women who carry an inherited hypercoagulable state. The indication of a lower or a lack of VTE risk associated with the use of progestin-only contraceptives and with transdermal HRT suggests that these therapies may be safer than combination oral contraceptive pills and oral HRT for women in whom oral estrogen therapy is considered contraindicated. Data that support such safety advantages are limited and should be interpreted with caution.

The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review.

BACKGROUND: Tamoxifen therapy for patients with breast carcinoma is perceived as an independent risk factor for venous thromboembolic events (VTE), but the risk associated with other adjuvant therapies is less well recognized. METHODS: The authors conducted a computerized PubMed literature search for English-language articles published between January 1966 and December 2003. Studies were analyzed with regard to trial design, breast carcinoma staging, adjuvant agent, definition of VTE outcomes, method of VTE case ascertainment, and the presence of concomitant VTE risk factors. RESULTS: Accurate determination of VTE rates was impaired by the universal lack of routine assessments for asymptomatic VTE. Therefore, only the risk of symptomatic VTE could be derived. The risk of VTE was increased twofold to threefold during tamoxifen or raloxifene use for breast carcinoma chemoprevention. It remains unknown whether the risk is increased further in women with inherited hypercoagulable states. In the setting of early-stage breast carcinoma, the risk of VTE is increased both with tamoxifen use and anastrozole use. Such risk appeared to be lower, albeit not negligible, with anastrozole. Significant methodologic limitations of all available studies in women with advanced-stage breast carcinoma precluded determination of the true VTE risk associated with different adjuvant hormonal agents and made it nearly impossible to compare the risk between different drugs. CONCLUSIONS: All agents used for breast carcinoma chemoprevention and adjuvant therapy appear to increase the risk of VTE. Available data were insufficient to support any assumptions that newer hormonal forms of hormone manipulation are safer than tamoxifen in women with advanced breast carcinoma.

Goal-oriented thrombolytic therapy for venous thromboembolic disease.

The goal of a therapeutic intervention should be to positively impact a meaningful patient outcome. Too often, though, efficacy of a treatment is based on a surrogate endpoint. Thrombolytic therapy for venous thromboembolic disease is an example of a treatment whose success is primarily based on radiographic or echocardiographic endpoints and not endpoints such as symptom relief, functional capacity, quality of life, thrombosis recurrence, and survival. Thrombolysis for lower-extremity deep venous thrombosis does not reduce the incidence of pulmonary embolism, has unclear impact on the rates of post-thrombotic syndrome, and is associated with increased rates of major hemorrhage compared to conventional anticoagulation. Reserving thrombolysis for limb-threatening thrombosis especially in the young seems prudent. Currently available evidence does not support the routine use of thrombolytic therapy in patients with hemodynamically stable pulmonary embolism regardless of right ventricular function status. Risks, benefits, and alternative therapies must always be considered, and therapy must be guided by individual case circumstances and the best available scientific evidence.

Patients with inferior vena caval filters should receive chronic thromboprophylaxis.

A 32-year-old man with testicular carcinoma is diagnosed with an acute left leg deep venous thrombosis (DVT) during his fourth cycle of combination chemotherapy. Because of anticipated moderate to severe thrombocytopenia, anticoagulation is initially avoided and an inferior vena cava (IVC) filter is placed to prevent pulmonary embolism (PE). After completion of all chemotherapy he is deemed to be in remission and anticoagulation is begun. The optimal duration of anticoagulation in this patient is pondered.

Estrogen-containing oral contraceptives are allowable in young women with factor V Leiden heterozygosity without a history of thrombosis.

An 18-year-old woman without significant past medical and surgical history presents to discuss the safety and efficacy of oral contraceptives. She is sexually active and currently relying on condoms alone for birth control. Her cousin had a deep venous thrombosis (DVT) following a pregnancy. As part of the family screening, this patient was identified as a factor V Leiden heterozygote. The risks and benefits of initiating oral contraceptives are discussed.

Hypercoagulable state testing and malignancy screening following venous thromboembolic events.

Mounting interest in hypercoagulability, increased availability of hypercoagulable state test 'panels' and enhanced ability to identify abnormalities in tested patients have prompted widespread testing. Testing for acquired and inherited hypercoagulable states uncovers an abnormality in over 50% of patients presenting with an initial venous thromboembolic event (VTE) but may have minimal actual impact on management in most of these patients. Such laboratory screening should be reserved for patients in whom the results of individual tests will significantly impact the choice of anticoagulant agent, intensity of anticoagulant therapy, therapeutic monitoring, family screening, family planning, prognosis determination, and most of all duration of therapy. Testing 'just to know' is neither cost-effective nor clinically appropriate. The most important testing in patients following acute VTE may be age- and gender-specific cancer screening. Cancer screening following VTE seems most prudent in older individuals and in those with idiopathic VTE and no laboratory evidence for an inherited hypercoagulable state. Cancer screening should focus on identification of treatable cancers and those where diagnosis in an early stage favorably impacts patient survival. Extensive searches for occult malignancy employing whole-body computed tomography and serum tumor markers may identify more cancers but without affecting patient outcome. We advocate that physicians should focus their attention more on VTE prophylaxis and proper treatment and less on costly and, at times, invasive testing of questionable value.

Diagnosis of venous thromboembolic disease in cancer patients.

Venous thromboembolic disease is a common but likely underdiagnosed condition in the cancer patient population. Timely and accurate diagnosis of venous thromboembolism is imperative due to the unacceptable morbidity and mortality associated with a misdiagnosis. Because diagnosis of the condition based on clinical grounds alone is unreliable, physicians should select an appropriate objective diagnostic test to confirm or refute their clinical impressions. Compression duplex ultrasound is the best initial imaging test for both suspected upper- and lower-extremity deep venous thrombosis. Magnetic resonance venography (MRV) is a valid alternative when ultrasound is inconclusive, but contrast venography remains the "gold standard." Suspected pulmonary embolism should be initially evaluated by helical (spiral) computed tomography (CT) or ventilation/perfusion lung scintigraphy, the former being preferred in cases of obvious pulmonary or pleural disease. Indeterminate studies should prompt performance of contrast pulmonary angiography. Inferior vena cava thrombosis is also best assessed by contrast venography, with MRV and CT reserved as alternative imaging modalities. Evidence to date suggests that D-dimer assays remain unreliable in excluding venous thromboembolism in cancer patients. A newer latex agglutination D-dimer assay may prove to be clinically useful in this setting.