A Meta-Analysis to Determine the Risk of Heparin Induced Thrombocytopenia (HIT) and Isolated Thrombocytopenia in Prophylaxis Studies Comparing Unfractioneted Heparin (UFH) and Low Molecular Weight Heparin (LMWH).

Abstract

HIT is an uncommon but potentially devastating complication of anticoagulation with UFH or LMWH. The absolute risk of HIT and thrombocytopenia are not clearly defined and no summary data to provide odds ratio is available. We conducted a meta-analysis to determine and compare the incidences of HIT in surgical or medical patients receiving thromboprophylaxis with either UFH or LMWH. We searched MEDLINE-OVID and MEDLINE-PubMed using and combining the following terms: heparin induced thrombocytopenia, low molecular weight heparin, prophylaxis, randomized controlled trials, prospective studies. The function Explode was used. Search was limited to humans from 1984 to 2004. Over 400 abstracts were reviewed and then 91 articles were independently reviewed by two authors, without any restriction of article language. Included studies were those comparing prophylactic UFH and LMWH and measuring HIT (defined as platelets drop > 50% or < 100 X 109/L AND positive laboratory HIT assay) or thrombocytopenia (defined as platelets drop > 50% or < 100 X 109/L) as outcomes. Studies defining thrombocytopenia with lower thresholds were excluded because cases could have been missed. Extracted data included patient characteristics, drug regimens, HIT, thrombocytopenia and venous thromboembolism rates. Disagreements were resolved by consensus. Eligible studies were included into the meta-analysis using a random-effects model to determine the odds ratio for the incidences of HIT and thrombocytopenia between UFH and LMWH. Funnel plots were made to assess possible publication bias. 17 articles were eligible with a total of 8500 patients: 2 RCTs measuring HIT; 10 RCTs measuring thrombocytopenia, and 5 prospective non-randomized studies with comparison groups measuring HIT. Three analysis were performed and all favoured the use of LMWH: 1) 2 RCTs measuring HIT showed an OR of 0.10 (95% confidence interval [CI] 0.01–0.77; p=0.03); 2) all 7 studies measuring HIT showed an OR of 0.11 (95%CI= 0.05–0.26; p< 0.00001); 3) 12 RCTs measuring thrombocytopenia showed an OR of 0.45 (95% CI= 0.26–0.80; p=0.006). Comparing the rates in the 7 studies measuring HIT UFH resulted in HIT in 3.4% (95%CI=2.6% to 4.3%) of cases and LMWH resulted in HIT in 0.2% (95% CI=0.1% to 0.6%), a statistically significant difference (p<0.0001). This meta-analysis confirms the lower incidences of HIT and thrombocytopenia with LMWH prophylaxis compared to UFH. Absolute rates of HIT with LMWH are very low. The HIT rates should be considered when determining the drug of choice for thromboprophylaxis in surgical and medical patients.

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

“…One record was an audit (Qureshi 2007). Thirty-nine records were reviews (Andreu 2009; Avvisati 2003; Benjamin 2002; Blajchman 2008; Buhrkuhl 2010; Casbard 2004; Cid 2007; Dzik 2004; Goodnough 2002; Goodnough 2005; Heal 2004; Heddle 2003; Heddle 2007; Jelic 2006; Levi 2002; Lordkipanidze 2009; Lozano 2003; Martel 2004; McNicol 2003; Paramo 2004; Poon 2003; Rabinowitz 2010; Rayment 2005; Razzaghi 2012; Roberts 2003; Sakakura 2003; Shehata 2009; Shen 2007; Slichter 2004; Slichter 2007; Slichter 2012; Sosa 2003; Strauss 2004; Strauss 2005; Tinmouth 2003; Wandt 2010; Wang 2005; Woodard 2002; Zeller 2014). Twenty-six studies were not RCTs (Aderka 1986; Callow 2002; Cameron 2007; Chaoui 2005; Chaurasia 2012; Decaudin 2004; Eder 2007; Elting 2002; Elting 2003; Friedmann 2002; Gil-Fernandez 1996; Gmür 1991; Greeno 2007; Hardan 1994; Lawrence 2001; Navarro 1998; Nevo 2007; Norol 1998; Paananen 2009; Sagmeister 1999; Verma 2008; Wandt 1998; Wandt 2005; Wandt 2006; Weigand 2009; Zahur 2002).…”

“…Thirty-nine records were reviews (Andreu 2009; Avvisati 2003; Benjamin 2002; Blajchman 2008; Buhrkuhl 2010; Casbard 2004; Cid 2007; Dzik 2004; Goodnough 2002; Goodnough 2005; Heal 2004; Heddle 2003; Heddle 2007; Jelic 2006; Levi 2002; Lordkipanidze 2009; Lozano 2003; Martel 2004; McNicol 2003; Paramo 2004; Poon 2003; Rabinowitz 2010; Rayment 2005; Razzaghi 2012; Roberts 2003; Sakakura 2003; Shehata 2009; Shen 2007; Slichter 2004; Slichter 2007; Slichter 2012; Sosa 2003; Strauss 2004; Strauss 2005; Tinmouth 2003; Wandt 2010; Wang 2005; Woodard 2002; Zeller 2014).…”

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

“…Thirty-six citations were reviews (including three systematic reviews): Andreu 2009; Avvisati 2003; Benjamin 2002; Blajchman 2008; Buhrkuhl 2010; Casbard 2004; Cid 2007; Dzik 2004; Goodnough 2002; Goodnough 2005; Heal 2004; Heddle 2003; Jelic 2006; Levi 2002; Lordkipanidze 2009; Lozano 2003; Martel 2004; McNicol 2003; Paramo 2004; Poon 2003; Rabinowitz 2010; Rayment 2005; Roberts 2003; Sakakura 2003; Shehata 2009; Shen 2007; Slichter 2004; Slichter 2007; Sosa 2003; Strauss 2004; Strauss 2005; Tinmouth 2003; Wandt 2010; Wang 2005; Woodard 2002; Zeller 2014…”

“…This study was included within the previous systematic review. This study compared different platelet component doses and has been excluded from this review Lapierre 2003 Comparison of standard apheresis platelet products vs a donor reduction policy Lawrence 2001 A non-randomised retrospective historical control study (different platelet transfusion thresholds) Leach 1991 Comparison of warmed vs standard platelet transfusions Lee 1989 Comparison of ABO -matched vs mismatched platelet transfusions Levi 2002 Review Lordkipanidze 2009 Review Lozano 2003 Review Lozano 2010 Efficacy of older platelet transfusions Lozano 2011 Comparison of pathogen -inactivated vs conventional platelet products Lu 2011 Comparison of low -dose platelet transfusion vs standard -dose platelet transfusion Martel 2004 Review McCullough 2004 Comparison of pathogen -inactivated vs conventional apheresis platelets McNicol 2003 Review Messerschmidt 1988 Comparison of HLA -matched vs mismatched platelet transfusions Mirasol 2010 Comparison of pathogen -inactivated vs conventional platelet products Murphy 1986 Comparison of HLA -matched vs leucodepleted blood products Navarro 1998 …”

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

“…One citation was an audit (Qureshi 2007). Thirty-nine citations were reviews (including four systematic reviews) (Andreu 2009; Avvisati 2003; Benjamin 2002; Blajchman 2008; Buhrkuhl 2010; Casbard 2004; Cid 2007; Dzik 2004; Goodnough 2002; Goodnough 2005; Heal 2004; Heddle 2003; Heddle 2007; Jelic 2006; Levi 2002; Lordkipanidze 2009; Lozano 2003; Martel 2004; McNicol 2003; Paramo 2004; Poon 2003; Rabinowitz 2010; Rayment 2005; Razzaghi 2012; Roberts 2003; Sakakura 2003; Shehata 2009; Shen 2007; Slichter 2004; Slichter 2007; Slichter 2012; Sosa 2003; Strauss 2004; Strauss 2005; Tinmouth 2003; Wandt 2010; Wang 2005; Woodard 2002; Zeller 2014). Twenty-six studies were not RCTs (Aderka 1986; Callow 2002; Cameron 2007; Chaoui 2005; Chaurasia 2012; Decaudin 2004; Eder 2007; Elting 2002; Elting 2003; Friedmann 2002; Gil-Fernandez 1996; Gmur 1991; Greeno 2007; Hardan 1994; Lawrence 2001; Navarro 1998; Nevo 2007; Norol 1998; Paananen 2009; Sagmeister 1999; Verma 2008; Wandt 1998; Wandt 2005; Wandt 2006; Weigand 2009; Zahur 2002).…”