Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association.

The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (n = 1,152 and n = 2,310) and identified signals at ABO (P < 7.9E-139) and VWF (P < 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12-2p13 (LOD score 5.3) and at the ABO locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the "missing heritability" for other complex genetic traits.

Pharmacomechanical catheter-directed thrombolysis for pregnancy-related iliofemoral deep vein thrombosis.

PURPOSE: Pharmacomechanical catheter-directed thrombolysis (PCDT) is relatively contraindicated during pregnancy and postpartum. The purpose of this study was to evaluate outcomes of PCDT in this population. MATERIALS AND METHODS: Data for 11 consecutive patients (aged 21-35 y) undergoing PCDT at a tertiary center for symptomatic pregnancy-related iliofemoral deep vein thrombosis (DVT) were retrospectively reviewed. Details regarding patient presentation, location and extent of thrombus, the PCDT procedure, outcomes, frequency of postthrombotic syndrome (PTS), and subsequent pregnancies were recorded. Two patients who presented in the first trimester terminated their pregnancies after PCDT, 2 patients who presented in the third trimester delayed PCDT until after delivery, and 7 patients who presented with postpartum DVT underwent immediate PCDT. RESULTS: Thrombus extended into the inferior vena cava in 5 patients (45%) and into popliteal/tibial veins in 7 (64%). Four patients (36%) had synchronous pulmonary embolism and three had May-Thurner compression. Median interval from diagnosis to PCDT was 5 days (range, 2-68 d); median duration of urokinase infusion was 27 hours (range, 16-72 h). Greater than 90% clot lysis was achieved in 9 of 11 patients (82%). Metal stents were placed in 8 of 11 patients (73%). A self-limiting popliteal hematoma developed in 1 patient, and 2 had early recurrent thrombosis requiring repeat PCDT. At median 20-month follow-up, nonocclusive thrombus was seen in 5 patients. No patient developed PTS. Three patients, all with stents, had uneventful pregnancies after PCDT. CONCLUSIONS: Pharmacomechanical catheter-directed thrombolysis achieved encouraging initial outcomes in this series. Validation in prospective trials with larger enrollment and longer follow-up is needed.

Heparin-induced thrombocytopenia in myeloproliferative disorders: a rare or under-diagnosed complication?

Patients with myeloproliferative disorders (MPD) are prone to develop thrombotic complications and thus frequently receive heparin. Surprisingly heparin-induced thrombocytopenia (HIT) has been rarely reported in MPD and is potentially under-diagnosed due to the relatively high platelet count. We report three patients with MPD who developed HIT; all presented with a relative fall of platelet counts (although without an absolute thrombocytopenia), thrombosis or skin necrosis and a positive test for HIT antibodies (particle gel immunoassay). Risk factors for developing HIT in our patients were exposure to unfractionated heparin, a recent surgical procedure and female gender. We review the literature on HIT in MPD and discuss the diagnosis of HIT in the absence of an absolute thrombocytopenia.

Exacerbation of pulmonary sarcoidosis after liver transplantation.

Patients with hepatic sarcoidosis rarely require orthotopic liver transplantation (OLT). Progression of granulomatous activity involving other organs after OLT has rarely been described. We describe a 32-year-old woman who underwent liver transplantation for sarcoidosis-associated end-stage liver disease. She presented 4 years later with shortness of breath, hilar lymphadenopathy, and interstitial lung abnormalities. Liver functions were normal. Open lung biopsy results revealed granulomata compatible with sarcoidosis. The patient made a complete recovery after corticosteroid treatment. To the best of our knowledge, this is a first description of severe exacerbation of pulmonary sarcoidosis in an immunosuppressed patient who underwent liver transplantation for sarcoidosis-associated liver disease.