Dalteparin
Fragmin
The workhorse anticoagulant in hospital practice: subcutaneous dosing once daily, predictable effect, and no need for routine monitoring, allowing home administration. The difference between the prophylactic dose and the therapeutic dose is fourfold and is expressed in IU — confusing the two is the most common dosing error. Unlike unfractionated heparin, dalteparin is eliminated renally, so at eGFR below 30 ml/min the effect accumulates and the dose must be adjusted or the drug changed.
Spinal or epidural puncture during ongoing treatment can cause spinal haematoma with permanent paralysis — therapeutic dosing requires at least 24 hours off before puncture or catheter removal, prophylactic dosing at least 12 hours. In severe renal failure dalteparin accumulates and bleeding risk increases without any change in APTT or PT.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Thromboprophylaxis, medical patient | 5 000 IU sc × 1 | 2 500 IU × 1 at low risk or weight below 50 kg |
| Thromboprophylaxis, orthopaedic surgery | 5 000 IU sc the evening before surgery, then 5 000 IU × 1 | alternatively 2 500 IU 1–2 h preoperatively and 2 500 IU 12 h later |
| Venous thromboembolism, treatment | 200 IU/kg sc × 1, maximum 18 000 IU/day | 100 IU/kg × 2 at increased bleeding risk or weight above 90 kg |
| Cancer-associated venous thromboembolism | 200 IU/kg sc × 1 for 30 days, then 150 IU/kg × 1 months 2–6 | documented superiority over warfarin in active cancer |
| Unstable coronary artery disease | 120 IU/kg sc × 2, maximum 10 000 IU per dose | in combination with aspirin, for up to 8 days while awaiting intervention |
eGFR ≥ 30 ml/min: no adjustment. eGFR < 30 ml/min: therapeutic dose should be reduced, given twice daily for more even exposure, and guided by anti-factor Xa; at eGFR < 20 ml/min or on dialysis, unfractionated heparin is often the safer choice. Prophylactic dose may need to be reduced when S-creatinine exceeds 150 μmol/l. Target anti-Xa at therapeutic dosing: 0,5–1,5 IU/ml, measured 4 hours after injection.
No established dose adjustment. Hepatic failure with coagulopathy, thrombocytopenia, or oesophageal varices implies increased bleeding risk and warrants a lower dose and more frequent blood count monitoring.
Used in children with weight-based dosing and stepwise adjustment in increments of 25 IU/kg until anti-Xa 0,5–1,0 IU/ml is reached in a sample taken 4 hours after injection. The youngest children require higher doses per kilogram. Initiated by a paediatric coagulation unit.
Protamine only partially reverses dalteparin — anti-Xa activity is neutralised to 25–50 % — so for a patient who may need rapid and complete reversal of anticoagulation, unfractionated heparin is the right choice from the outset. Do not confuse the prophylactic dose with the therapeutic dose: 5 000 IU in an 80 kg patient with pulmonary embolism is a quarter of what is required, and that undertreatment is discovered only at recurrence. Do not give dalteparin to a patient with previous heparin-induced thrombocytopenia — cross-reactivity with unfractionated heparin is high.
Pharmacokinetics
- BIOAVAIL.
- ~90 % subcutaneously
- Vd
- 40–60 ml/kg
- t½
- 3–4 h sc, 2 h iv — prolonged in uraemia
- MEAN MW
- ~6 000 dalton
- ANTI-Xa/ANTI-IIa
- ~2,7:1
- METABOLISM
- Depolymerisation, no CYP metabolism
- EXCRETION
- Renal
- PEAK EFFECT
- 3–4 h after subcutaneous injection