Background
Methods
Performed searches
Study selection
Quality assessment
Data extraction
Statistical analysis
Sensitivity analyses
Results
Identification and study selection
Characteristics of studies and patients
Study | Year | Country | Follow-up | Patients enrolled (n) LMWH/UFH (n/n) | Drop-outs (n) LMWH/UFH (n/n) | LMWH type | LMWH mean dose | UFH mean dose | HD/HDF |
---|---|---|---|---|---|---|---|---|---|
Cross-over randomized design | |||||||||
Cianciolo et al. [16] | 2011 | Italy | 2 months | 40 | 0 | Nadroparin | 64 IU/kg | bolus 50 IU/kg and 30 IU/kg/h | HD |
Klejna et al. [29] | 2014 | Poland | 6 months | 21 | 0 | Enoxaparin | 5280 IU ± 1120 IU | 4881 IU ± 1916.3 IU | HD |
Lord et al. [22] | 2002 | Canada | 2 months | 32 | 2 | Tinzaparin | 4318.2 IU ± 702.8 IU | 8207.9 IU ± 2530.9 IU | HD |
Saltissi et al. [24] | 1999 | Australia | 6 months | 36 | 5 | Enoxaparin | 100 IU/kg | bolus 50 IU/kg and 1000 IU/h | HD |
Stefoni et al. [27] | 2002 | Italy | 36 months | 54 | 7 | Nadroparin | 64 IU/kg | bolus 1500 IU and 1500 IU and 1500 IU ± 500 IU perfusion | HDF |
Cross-over non-randomized design | |||||||||
Al-Saran et al. [13] | 2010 | Saudi Arabia | 12 months | 23 | 0 | Tinzaparin | 2000–3000 IU | 5000 IU | HD |
Bambauer et al. [14] | 1990 | Germany | 12 months | 27 | 6 | Dalteparin | 4216 IU ± 2237 IU | 4958 IU ± 2561 IU | HD |
Bramham et al. [15] | 2008 | United Kingdom | 4 months | 110 | 2 | Tinzaparin | 2500–5000 IU | 1000 IU ± 500–2000 IU | HDF |
Deuber et al. (part 1) [17] | 1991 | Germany | 60 months | 5 | 0 | Non specified | Non specified | 29–143 IU/kg | HD |
Deuber et al. (part 2) [17] | 1991 | Germany | 24 months | 5 | 0 | Non specified | Non specified | 29–143 IU/kg | HD |
Kronenberg et al. [19] | 1995 | Austria | 12 months | 24 | 0 | Certoparin | 44.7 IU/kg ± 21.5 IU/kg | 25.1 IU/kg ± 7.8 IU/kg | HD |
Lai et al. [20] | 2001 | China | 24 months | 40 | 6 | Nadroparin | 4100–6150 IU | 5000–7000 IU | HD |
Leu et al. [21] | 1998 | Taiwan | 4 months | 20 | 0 | Dalteparin | 2413 IU ± 954 IU | 2413 IU ± 954 IU | HD |
Schmitt et al. [25] | 1993 | Germany | 12 months | 22 | 0 | Dalteparin | bolus 1500 IU and 675 IU/h ± 284 IU/h | bolus 1500 IU and 1031 IU/h ± 342 IU/h | HD |
Yang et al. (part 1) [28] | 1998 | Taiwan | 1 month | 10 | 0 | Fraxiparin | 10,000 ICU | bolus 1800 IU ± 675 IU and 895 IU/h ± 340 IU/h | HD |
Yang et al. (part 2) [28] | 1998 | Taiwan | 12 months | 10 | 2 | Fraxiparin | 192.9 ICU/kg ± 3.8 ICU/kg | bolus 1800 IU ± 675 IU and 895 IU/h ± 340 IU/h | HD |
Randomized parallel design | |||||||||
Elisaf et al. [18] | 1997 | Greece | 12 months | 76 38/38 | 0 | Tinzaparin | 3000 IU | 5000–7000 IU | HD |
Nurmohamed et al. [23] | 1991 | The Netherlands | 6 months | 70 35/35 | 13 8/5 | Nadroparin | 150–200 IU/kg | bolus 2500 IU and 600–2200 IU/h | HD |
Schrader et al. [26] | 1988 | Germany | 12 months | 70 35/35 | 8 5/3 | Dalteparin | bolus 36.8 IU/kg ± 17.3 IU/kg and 12.2 IU/kg/h ± 5.0 IU/kg/h | bolus 58.3 IU/kg ± 26.3 IU/kg and 16.6 IU/kg/h ± 6.7 IU/kg/h | HDF |
Study | Mean age + SD (years) | Age range (years) | Male/Female (n/n) | Dialysis duration and frequency | Inclusion criteria | Exclusion criteria |
---|---|---|---|---|---|---|
Cross-over with randomization | ||||||
Cianciolo et al. | 63.3 ± 7.2 | 42–72 | 21/19 | 4 h 3×/wk | chronic HD, age 18+, stable, AVF | gastrointestinal bleeding, acute cardiovascular event 3 months before, malignancy, coagulation disorders, DVT, immunosupressive therapy, acute vasculitis, liver disease, active infection, diabetes, enrolled in other clinical trial |
Klejna et al. | 68.2 | 44–82 | 11/10 | 4–5 h 3×/wk | Chronic HD | HIV, Hepatitis B, Hepatitis C, VTE, gastrointestinal bleeding, coagulation disorders |
Lord et al. | 66.6 ± 14.8 | NS | 17/15 | 4 h 3×/wk | Chronic HD | Patients with catheters, with bleeding diathesis in last 3 months, with thrombocytopenia, hepatic failure, oral anticoagulation (but not antiplatelets) |
Saltissi et al. | NS | 22–85 | 17/19 | 3–5 h 3×/wk | Chronic HD | bleeding disorders, anticoagulation therapy (warfarin, aspirin) |
Stefoni et al. | 63.7 ± 7 | NS | 39/15 | 4 h 3×/wk | Chronic HD for at least 12 months | active gastrointestinal bleeding, myeloproliferative disorders, malignant diseases, hereditary deficiency of coagulation factors, LAC phenomenon, antiphospholipid syndrome |
Cross-over without randomization | ||||||
Al-Saran et al. | 46.83 ± 14.63 | NS | 17/6 | 3–4 h 3×/wk | at least 6 months on HD prior to study | bleeding disorders, anemia with hemoglobin levels less than 10 g/dL, recent trauma, surgery, infectious disease or hemorrhagic disorder (< 1 month) in addition to those receiving oral or other forms of anticoagulant therapy (e.g. warfarin, aspirin), or drugs that could affect heparin activity (e.g. tetracyclines, digitalis, and antihistamines) |
Bambauer et al. | 60 | NS | 12/15 | NS | Chronic HD | NS |
Bramham et al. | 61 ± 15 | NS | 65/45 | 3–4 h 3×/wk | Chonic HD on monitoring shift | Renal transplant, transferred to satellite unit, switched to PD, on warfarin |
Deuber et al. (part 1) | 53 ± 7 | 47–65 | NS | 4 h 3×/wk | chronic HD for at least 18 months | NS |
Deuber et al. (part 2) | 50 ± 18 | 20–67 | NS | 4 h 3×/wk | chronic HD for at least 18 months | NS |
Kronenberg et al. | 44.7 ± 16.8 | NS | 13/11 | 3.5–5 h 3×/wk | in pre-dialysis | diabetes, bleeding disorders, oral anticoagulants, lipid lowering drugs |
Lai et al. | 42.2 ± 5.2 | 24–60 | 25/15 | 10–16 h/wk | Chronic HD | diabetes, primary hyperlipidemia |
Leu et al. | 57.8 ± 9.8 | NS | 7/13 | 4 h 3×/wk | Chronic HD at least 6 months | pts with lipid lowering drugs except non-diabetic pts. under lovastatin for >6 months, known hemorrhagic diathesis, low platelet count, liver insufficiency, hypersensitivity to heparin |
Schmitt et al. | 58.6 | 37–72 | 13/9 | 4–5.8 h | chronic HD, cholesterol >200 mg/dL | diabetes, concomittant drug treatment (lipid lowering drugs, COX inhibitors) |
Yang et al. (part 1) | 44 ± 15 | NS | 7/3 | 3×/wk | chronic HD, non diabetic | NS |
Yang et al. (part 2) | 57 ± 6.4 | NS | 7/3 | 3×/wk | chronic HD with diabetes type II | NS |
Parallel with randomization | ||||||
Elisaf et al. | NS | 15–61 | NS | 4 h 3×/wk | chronic HD | diabetes, hyperlipidemia (primary or secondary) |
Nurmohamed et al. | NS | NS | NS | 4–6 h 2-3×/wk | chronic HD | NS |
Schrader et al. | 54.0 ± 15.2 (LMWH) 51.6 ± 17.9 (UFH) | NS | 21/14 (LMWH) 19/16 (UFH) | NS | pre-HD requiring HD, not on heparin in prior 3 months | bleeding disorders, needed antiplatelets or anticoagulants |
Quality assessment
Synthesis of individual studies results
Study, year | Total bleeding events LMWH (n/N) | Total bleeding events UFH (n/N) | RR (95% CI) | Comments |
---|---|---|---|---|
Al-Saran et al. | 3/23 | 0/23 | 7.00 (0.38–128.33) | 3 minor bleedings with LMWH, controlled with dose adjustment |
Bambauer et al. | 3/27 | 6/27 | 0.50 (0.14–1.80) | No indication if minor or major bleeding events |
Bramham et al. | 0/110 | 4/110 | 0.11 (0.01–2.04) | 4 minor bleeding episodes with UFH |
Lord et al. | 3/32 | 8/32 | 0.38 (0.11–1.29) | LMWH: 1 major and 2 minor bleedings; UFH: 8 minor bleedings |
Nurmohamed et al. | 3/35 | 0/35 | 7.00 (0.37–130.69) | 3 minor bleeding events with LMWH |
Saltissi et al.a
| 12/36 | 6/36 | 2.00 (0.84–4.75) | LMWH:1 major and 11 minor bleedings; UFH: 6 minor bleedings |
Stefoni et al. | 0/54 | 7/54 | 0.07 (0.00–1.14) | 7 minor bleeding events with UFH |
Schrader et al.b
| 0/35 | 0/35 | excluded | n/a |
Yang et al. (part 1)b
| 0/10 | 0/10 | excluded | n/a |
Summary | 24/362 | 31/362 | 0.76 (0.26–2.22) |
Study | LMWH | UFH | |
---|---|---|---|
mean change, SD (mg/dl) | mean change, SD (mg/dl) | WMD (95% CI) (mg/dl) | |
Al-Saran et al.a
| −30.94 ± 39.52 | −20.11 ± 44.69 | −10.83 (−35.21, 13.55) |
Elisaf et al. | −18 ± 36.86 | −2 ± 32.78 | −16.00 (−31.69, −0.31) |
Kronenberg et al. | 12.3 ± 36.68 | −16.5 ± 33.84 | 28.80 (8.83, 48.77) |
Lai et al.a
| −2.70 ± 36.93 | −6.57 ± 45.82 | 3.87 (−14.37, 22.11) |
Leu et al.a
| −35.96 ± 35.03 | 31.71 ± 36.80 | −67.67 (−89.94, −45.40) |
Saltissi et al.a
| 0.39 ± 29.01 | 1.55 ± 30.55 | −1.16 (−14.92, 12.60) |
Schmitt et al. | −27 ± 51.10 | 21 ± 48.12 | −48.00 (−77.33, −18.67) |
Summary | −14.88 (−36.27, 6.51) |