Treatment of high-risk venous thrombosis patients using low-dose intraclot injections of recombinant tissue plasminogen activator and regional anticoagulation.

Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk.

Biochemical dynamics relevant to the safety of low-dose, intraclot alteplase for deep vein thrombosis.

Intraclot tissue plasminogen activator (tPA) has been shown to be an effective treatment for deep vein thrombosis (DVT) (Radiology 2008;246:619 and J Vasc Interv Radiol 2011;22:1107). We sought to correlate pharmacokinetics of tPA, fibrinogen, fibrinolytic inhibitors, and D-dimers with the safety and efficacy of intraclot tPA. Thirty subjects received intraclot tPA for lower extremity DVT by infiltrating the thrombus with ≤10 mg doses tPA in an open-label study, using a pulse-spray catheter.

Low-dose, once-daily, intraclot injections of alteplase for treatment of acute deep venous thrombosis.

Purpose: To evaluate the safety and efficacy of once-daily intraclot injections of low doses (≤ 10 mg) of tissue plasminogen activator (tPA) for thrombolysis of venous thrombosis.

Materials And Methods: In prospective studies, 33 patients with subclavian, jugular, and central venous thrombosis (SJ-CVT) (all but two cases associated with central catheters) were treated once a day with ≤ 4 mg/day of tPA, and 30 patients with acute deep vein thrombosis of the lower extremity (DVT-LE) < 14 days old were treated once a day with ≤ 10 mg/leg/day of tPA by intraclot "lacing" of thrombus without continuous infusions of tPA.

Results: Patency was restored in 26 (79%) of 33 patients with SJ-CVT using an average total dose of 7.

Individualized treatment for iron-deficiency anemia in adults.

Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption.

In vitro characterization of a monoclonal IgG(kappa) from a patient with planar xanthomatosis.

Objective: To characterize a monoclonal IgG(kappa) (MAb) from a patient with planar xanthoma that precipitated with serum lipids at reduced temperature.

Methods: The molecular weight (Mr), sensitivity to proteases, and glycosylation of the purified MAb were analyzed. The specificity of the MAb was tested by measuring cryoprecipitation with pure high- (HDL) and low-density (LDL) lipoproteins.

Deep vein thrombosis of lower extremity: direct intraclot injection of alteplase once daily with systemic anticoagulation--results of pilot study.

Purpose: To prospectively evaluate the outcome of patients with acute deep vein thrombosis (DVT) of the lower extremity treated with "lacing" of the thrombus with alteplase (recombinant tissue plasminogen activator, or rTPA).

Materials And Methods: This HIPAA-compliant study was approved by the Institutional Review Board of the National Heart, Lung, and Blood Institute and was funded by the National Institutes of Health. After giving written consent, 20 patients with first-onset acute DVT were treated with direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per leg per day; maximum of four treatments) and full systemic anticoagulation.

Cardiovascular manifestations of hypereosinophilic syndromes.

The hypereosinophilic syndromes (HESs) are characterized by persistent marked eosinophilia (>1500 eosinophils/mm(3)), the absence of a primary cause of eosinophilia (such as parasitic or allergic disease), and evidence of eosinophil-mediated end organ damage. Cardiovascular complications of HES are a major source of morbidity and mortality in these disorders. The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis.

The impact of major surgery on blood coagulation factors and thrombin generation.

We studied the blood coagulation system of 14 patients with metastatic malignancies before and after they had undergone major surgery. In addition to measuring a battery of coagulation factors, we assessed the function of the system with assays of whole blood thrombin generation. With the exceptions of factor VIII (fVIII), which increased, and fibrinogen and fIX, which did not change, the activities of all the pro- and anticoagulant proteins were significantly lower postoperatively.

Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes.

Background: High serum vitamin B12 concentrations have been reported in patients with hepatic disease, disseminated neoplasia, myeloproliferative disorders, and hypereosinophilic syndromes. We recently discovered an extraordinarily increased vitamin B12 concentration in a patient without these underlying conditions.

Methods: Affinity and size-exclusion chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and ELISA methods were used to determine the cause of the increased vitamin B12 concentrations in this patient's serum.

Venlafaxine-induced ecchymoses and impaired platelet aggregation.

Objective: To describe a case of venlafaxine-induced ecchymoses.

Methods: A patient with a history of ecchymoses coincident with venlafaxine therapy was rechallenged with the drug. Her platelet function was assessed with aggregation and ATP release studies before the rechallenge and after she developed ecchymoses.

Use of heparin versus lepirudin flushes to prevent withdrawal occlusion of central venous access devices.

Study Objective: To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices.

Design: Randomized, double-blind clinical trial.

Setting: Research institution-tertiary referral center.

The effect of red blood cells on thrombin generation.

We have developed an assay of thrombin generation in clotting whole blood. Because our goal was to study patients with red blood cell diseases that are associated with thrombosis, the initial evaluation of this assay analysed the effect of the haematocrit and haemolysate on the total amount of thrombin activity generated and the maximal concentration of thrombin achieved. Both of these parameters were proportional to the haematocrit throughout a wide range of clinically relevant cell concentrations.

Factor V Leiden as a common genetic risk factor for venous thromboembolism.

Purpose: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism.

Organizing Framework: An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated.

Findings: FVL is the most commonly recognized genetic trait associated with venous thrombosis.

Disseminated intravascular coagulation in an ambulatory young woman.

We are reporting the case of an ambulatory young woman with a 10-year history of recurrent venous thrombosis who presented to us with diffuse intravascular coagulation (DIC). After excluding the recognized causes of DIC, we examined the possibility that her clinically quiescent ulcerative colitis might be the underlying stimulus. We documented sepsis-range endotoxemia in this patient at a time when she was afebrile and had a normal C-reactive protein level.

Plasminogen interaction with platelets: the importance of carboxyterminal lysines.

Introduction: Thrombin stimulation enhances plasminogen binding to platelets and promotes platelet-dependent plasmin generation. The objective of this study was to determine whether carboxyterminal lysines (C-lysines) are important for these processes, as they are in other cell types.

Materials And Methods: 125I-plasminogen and varying concentrations of unlabeled plasminogen were added to washed platelets that were either resting or stimulated with thrombin, thrombin receptor activating peptide, or ADP.

Is thyroid hormone suppression therapy prothrombotic?

The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1 + 2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P < 0.

Retention of lepirudin at the tip of a silicone catheter: a better catheter flush solution?

Because central venous catheters often become blocked by clot at their tip despite heparin flushes, a more effective anticoagulant is needed. We hypothesize that lepirudin, a recently introduced protein anticoagulant, might be more effective than heparin because of its tendency to adsorb to silicone, a commonly used catheter material. We preliminarily tested this hypothesis in vitro by measuring residual lepirudin and heparin activity at the tip of a catheter that had been submerged in a flowing stream of water for various periods of time.

Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.

Study Objective: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide.

Design: Retrospective analysis of a randomized phase II trial.

Setting: National Institutes of Health clinical research center.

Parameters of coagulant and fibrinolytic capacity and activity in postmenopausal women: within-subject variability.

We have analyzed the within-subject variability of a battery of parameters of coagulant and fibrinolytic capacity and activity in postmenopausal women. We observed large differences in within-subject variability among the tests and have demonstrated how such data can be used to estimate the number of times a parameter must be measured to produce a statistically adequate sample.