Biomedical subjects
Publications and source records attributed to Steven R Deitcher.
Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT). We describe 2 cases of HIT and thrombosis in children with heart disease, including one that required extracorporeal membrane oxygenation. Lepirudin, dosed in the recommended adult weight--based fashion, was an effective antithrombotic agent in pediatric patients with HIT.
Detection of the prothrombin G20210A mutation was performed on the LightCycler Instrument (Roche Molecular Biochemicals, Mannheim, Germany) using commercially available primers and hybridization probes. Herein we report four cases from unrelated African American individuals where LightCycler analysis showed atypical melting curves. Sequence analysis of the four samples showed heterozygosity for a C to T mutation 1 bp upstream from the known 20210 mutation at position 20209. The clinical significance of this mutation is not known, but three patients in whom it was detected had a history of venous thrombosis or stroke. The fourth patient had severe liver disease, which may have masked thrombotic predisposition. Since most assays used to detect the G20210A mutation use a PCR/restriction digestion assay, which would not detect the C20209T mutation, this new mutation may be underrecognized when prothrombin gene mutation testing is performed by PCR/restriction digestion assay.
Acquired hemophilia A is a life-threatening immune-mediated hemorrhagic disorder that is most often found in individuals older than 50 who present with an unexplained activated partial thromboplastin time (aPTT) prolongation and clinically significant bleeding. The prolonged aPTT associated with acquired hemophilia A reflects factor VIII activity deficiency due to neutralizing or clearing autoantibodies. Deep venous thrombosis, in contrast, is a veno-occlusive disorder associated with several distinct hypercoagulable states that can result in significant morbidity and mortality due to pulmonary embolism, thrombus extension, and the post-thrombotic syndrome. A prolonged aPTT in the setting of thrombosis may reflect the presence of a lupus anticoagulant. In the absence of accurate diagnosis and the immediate institution of specific therapy, both disorders can be fatal. Three cases of acquired factor VIII inhibitors that included a prolonged aPTT, bleeding, and duplex ultrasound evidence of deep venous thrombosis are presented. The diagnostic and therapeutic challenges posed by these cases as well as a proposed mechanism by which pathologic thrombosis can develop in a patient with a life-threatening bleeding disorder are discussed.
Deep venous thrombosis (DVT) involving the upper extremities, chest, and neck has become appreciated as a significant cause of morbidity, especially in individuals with central venous access devices (CVAD). Like DVT involving the leg and pelvic veins, axillo-subclavian vein thrombosis can result in pulmonary embolism, post-thrombotic syndrome, and venous limb gangrene. Data relating to the natural history of internal jugular vein thrombosis (IJVT) is lacking. Risk factors, treatment patterns, and clinically relevant outcomes were retrospectively assessed in 74 consecutive patients with isolated IJVT. All patients (median age 66 years; range 36-80) had CVAD-associated IJVT, 22 (29.7%) had a history of cancer, and 14 (18.9%) had a history of prior DVT. Thirty-two (43.2%) were treated with systemic anticoagulation, 2 (2.7%) received a superior vena cava filter, and 40 (54.1%) received no specific therapy. Of the patients who underwent serial imaging, 7/40 (17.5%) had thrombus propagation. Two (2.7%) patients were diagnosed with pulmonary embolism, 8 (10.8%) were diagnosed with malignancy during a median follow-up of 20 months (range 18-24), and 3/53 (5.7%) suffered a recurrent DVT. Outcomes similar to those seen in leg DVT were observed. The most effective treatment strategy remains to be determined, but anticoagulant treatment was associated with a trend towards reduced all-cause mortality.
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No single imaging study or blood test is 100% sensitive and specific for pulmonary embolism. A combination of pretest clinical probability assessment, noninvasive pulmonary imaging (V/Q scanning or spiral CT), and D-dimer testing seems prudent before pursuing pulmonary angiography.
Arterial and venous thromboembolic events, including myocardial infarction, ischemic stroke, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism are common potentially life-, organ-, and limb-threatening vascular diseases. Anticoagulant therapy is recommended in these settings to prevent further thrombosis pending gradual clearance of the thrombotic occlusion by the endogenous fibrinolytic system. Recognition of the importance of the fibrinolytic system in thrombus resolution has resulted in the development of pharmacologic fibrinolytic (thrombolytic) agents to facilitate rapid restoration of vascular patency. Several plasminogen activator (PA) thrombolytic agents with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic disease. Newer PAs have been developed as "fibrin-specific", bolus-administration drugs to primarily treat acute coronary syndromes. Continuous infusions of these fibrin-specific PAs have become popular for the lysis relatively larger peripheral vascular thromboses. Loss infusion of newer tissue-type plasminogen activator-based PAs may result in an increased risk of bleeding, including intracranial hemorrhage. Currently available data fail to provide compelling evidence that newer PAs offer significantly greater efficacy and safety than well-established agents like urokinase when used to treat peripheral vascular thrombosis.
Standard venous thromboembolic event (VTE) treatment practices including the use of intravenous unfractionated heparin (UFH) for initial anticoagulation, oral warfarin for chronic anticoagulation, and the prescription of only 3 to 6 months total therapy may not be optimal in the setting of active cancer and ongoing anti-cancer therapy. Challenges of VTE management in cancer patients include heparin resistance due to excess circulating acute-phase proteins, increased recurrence rates during and following standard-intensity warfarin therapy, limited venous access to support therapeutic monitoring, and anticoagulation intensity-independent increased bleeding rates during anticoagulation. Bleeding during anticoagulation is of particular concern in the treatment of cancer patients with disease- or chemotherapy-related thrombocytopenia, central nervous system involvement, or recent invasive procedures. Low-molecular weight heparins (LMWH) have been shown to be at least as effective and safe for initial anticoagulation compared with UFH in persons with acute VTE and have gained popularity in the setting of VTE in cancer. LMWHs have the advantage of less non-specific protein binding, subcutaneous weight-based dosing without the need for monitoring in most cases, and probably less heparin-induced thrombocytopenia. Recent trials have demonstrated efficacy superiority of select LMWHs in place of oral warfarin for long-term anticoagulation in the cancer patient. The potential for anti-tumor effects and a survival advantage associated with select classes of anticoagulant agents is actively being investigated.
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