Eliot C. Williams

Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies

Background: Knowledge of independent, baseline risk factors for catheter‐related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis. Objectives: We conducted a meta‐analysis of individual patient‐level data to identify these baseline risk factors. Patients/Methods: MEDLINE, EMBASE, CINAHL, CENTRAL, DARE and the Grey literature databases were searched in all languages from 1995 to 2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient‐level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: A total sample of 5636 subjects from five RCTs and seven prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICCs), decreased CRT risk (OR, 0.43; 95% CI, 0.23–0.80), whereas past history of deep vein thrombosis (DVT) (OR, 2.03; 95% CI, 1.05–3.92), subclavian venipuncture insertion technique (OR, 2.16; 95% CI, 1.07–4.34) and improper catheter tip location (OR, 1.92; 95% CI, 1.22–3.02), increased CRT risk. Conclusions: CRT risk is increased with use of PICCs, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings.

Epsilon-Aminocaproic Acid in the Treatment of Patients with Acute Promyelocytic Leukemia and Acquired Alpha-2-Plasmin Inhibitor Deficiency

Patients with acute promyelocytic leukemia often develop bleeding diatheses during treatment. In seven patients who had this disease, the plasma level of alpha-2-plasmin inhibitor was the best predictor of severity of coagulopathy and bleeding. Clinical bleeding occurred when alpha-2-plasmin inhibitor levels measured less than 30% of normal levels. Patients with acute promyelocytic leukemia who had acquired deficiencies of alpha-2-plasmin inhibitor were considered to have deficits similar to those in persons congenitally deficient in alpha-2-plasmin inhibitor, and were assumed to be at increased risk for bleeding. Treatment with the fibrinolytic inhibitor, epsilon-aminocaproic acid, along with heparin resulted in prompt cessation of bleeding, reversal of laboratory evidence of fibrinolysis, and a decreased need for blood product support. The only thrombotic complication--thrombosis around a central venous catheter--resolved when treatment with epsilon-aminocaproic acid was discontinued. Epsilon-aminocaproic acid is a safe and effective therapy for those patients with acute promyelocytic leukemia who develop coagulopathy associated with low levels of alpha-2-plasmin inhibitor.

Anticoagulant effects of sulphonated polyurethanes.

Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma.

Cerebral Venous Thrombosis and Activated Protein C Resistance

BACKGROUND Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT. CASE DESCRIPTIONS We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons. CONCLUSIONS Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.

Coagulation Concepts Update

OBJECTIVE Since the previous comprehensive radiology review on coagulation concepts that was done in 1990, many studies have been published in the medical and surgical literature that can guide the approach of a radiology practice. The purpose of this article is to provide an analysis of these works, updating the radiologist on proper use and interpretation of coagulation assessment tools, medications that modify the hemostatic system, and the use of transfusions prior to interventions. CONCLUSION The basic tools for coagulation assessment have not changed; however, results from subspecialty research have suggested ways in which the use of these tools can be modified and streamlined to safely reduce time and expense for the patient and the health care system.

Cerebral venous thrombosis due to heparin-induced thrombocytopenia.

A patient with polycythemia vera who was treated with heparin for superficial septic thrombophlebitis developed heparin-induced thrombocytopenia and cerebral venous thrombosis with superior sagittal sinus occlusion 11 days after the institution of heparin therapy. We suggest that the severe thrombotic response to the heparin-induced platelet disorder in this patient occurred because the polycythemia vera and the purulent infection enhanced the thrombophilia caused by heparin-induced thrombocytopenia. This condition can be avoided in most instances if heparin is used for no longer than 5 days.

Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2

This study was performed to determine the incidence of central venous device‐related blood stream infection and thrombosis in patients treated with moderate dose continuous‐infusion interleukin‐2 (IL‐2).

Fibrinolysis and acquired alpha-2 plasmin inhibitor deficiency in amyloidosis

A patient with plasma cell myeloma and amyloidosis presented with a severe bleeding disorder. There was laboratory evidence of fibrinolysis and severe deficiency of alpha-2 plasmin inhibitor. Treatment with epsilon aminocaproic acid was associated with diminished bleeding and marked increase in the plasmin inhibitor level. This is the first report of acquired alpha-2 plasmin inhibitor deficiency in the fibrinolytic state associated with amyloidosis.

Cerebral venous thrombosis with plasminogen deficiency.

We describe a patient with inherited plasminogen deficiency who developed extensive cerebral venous thrombosis. Several other conditions that might have contributed to a hypercoagulable state, including mild thrombocytosis, thyrotoxicosis, and a chronic inflammatory lung disorder, were present. We also discuss the evidence linking plasminogen deficiency with a thrombophilic state. The diagnosis of cerebral venous thrombosis in this case was readily established by nuclear magnetic resonance imaging, a technique that is ideally suited for the evaluation and follow-up of patients with this condition.