title: Inverse relationship of bleeding risk with clot burden during pulmonary embolism treatment with LMW heparin.
abstract: BACKGROUND
  Clinically relevant bleeding occurs three times as frequently as recurrent venous thromboembolism in the modern early treatment of pulmonary embolism (PE) with fixed-dose, unmonitored anticoagulants. Unfractionated heparin (UFH) is monitored and adjusted to assure efficacy and minimize bleeding risk, but low molecular weight heparin (LMWH) is not. PE requires more anticoagulant than isolated deep venous thrombosis. Speculating that PE with low clot burden could lead to excess bleeding with unadjusted LMWH treatment but not with UFH, we compared PE patients receiving either UFH or LMWH with high and low clot burden for clinically significant bleeding in an observational study.
  
  
  METHODS
  Patients with acute PE at multiple Chinese teaching hospitals had been randomized to UFH or LMWH for initial treatment. These treatment cohorts had baseline measurement of pulmonary artery obstruction (PAO) score, which was prospectively separated into quartiles, lowest to highest PAO. All patients were followed for bleeding episodes, which were subsequently analyzed by quartile of PAO.
  
  
  RESULTS
  Two hundred seventy-four patients divided between the two groups had similar efficacy and safety outcomes (12 clinically significant bleeds in the UFH group vs 15 in the LMWH group). LMWH recipients with the smallest clot burdens (lowest PAO quartiles) had highest bleeding rates (Cochran-Armitage trend test, P trend = 0.048), but there was no such trend for UFH recipients.
  
  
  CONCLUSIONS
  For UFH, excess anticoagulant pro-hemorrhagic potential is down-adjusted via activated partial thromboplastin time monitoring, but for LMWH it is not. For PE patients at high bleeding risk, UFH may be safer if the clot burden is small.
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. cyh-birm@263.net.|Beijing Hospital, Ministry of Health, Beijing, China. cyh-birm@263.net.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Yuanhua
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Affiliated Hospital of Medical College of Qingdao, Shandong, China.
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Sir Run Run Shaw Hospital, Affiliated with Zhejiang University, Zhejiang, China.
authors.forename: Kejing
authors.initials: K
authors.lastname: Ying
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Liang
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Weixuan
authors.initials: W
authors.lastname: Lu
authors.affiliation: The Affiliated Hospital of Dalian Medical University, Liaoning, China.
authors.forename: Zhonghe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiansheng
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ying Hu
authors.initials: YH
authors.lastname: Shen
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin
keywords: bleeding; heparin; low molecular weight heparin; pulmonary artery; pulmonary embolism