After SC injection, LMWHs are better absorbed than unfractionated heparin, and bind less to proteins in plasma and in the endothelial wall. As a result they have around 90% bioavailability compared with 10–30%
with unfractionated heparin.After SC injection, the plasma half-life of LMWHs is around 4 hours, enabling a single dose to provide effective anti-coagulant activity for up to 24 hours in the treatment of venous thromboembolism, peri- and postoperative surgical thomboprophylaxis, and the prevention of clotting in the extracorporeal circulation during haemodialysis or haemofiltration.
The incidence of bleeding is similar between LMWHs and unfractionated heparin.The incidence of immune-mediated thrombocytopenia is about 2–3% of patients treated with unfractionated heparin, typically developing after 5–10 days’ treatment. In clinical trials with dalteparin, thrombocytopenia occurred in up to 1% of patients receiving treatment for unstable angina, undergoing abdominal surgery or hip replacement surgery. LMWHs are preferred over unfractionated heparin because they are as effective, simplify treatment (once-daily dosing, no IV cannulation), have a lower risk of heparin-induced thrombocytopenia and monitoring is not required.
Uses:
Prophylaxis of DVT
Treatment of DVT and pulmonary embolism or both
Unstable angina
Prevention of clotting in extracorporeal circuits
Contraindications:
Generalised bleeding tendencies
Acute GI ulcer
Cerebral haemorrhage
Subacute endocarditis
Heparin-induced immune thrombocytopenia
Injuries to and operations on the CNS, eyes and ears
Known haemorrhagic diathesis
Hypersensitivity to dalteparin or other LMWHs and/or heparins
Administration:
• Peri- and post-operative surgical prophylaxis – moderate risk 2500 units only daily SC
• Peri- and post-operative surgical prophylaxis – high risk 5000 units only daily SC
• Prophylaxis of DVT in medical patients 5000 units only daily SC
• Treatment of DVT and pulmonary embolus or both Start dalteparin with oral warfarin (as soon as possible) until INR in therapeutic range. 200 units/kg once daily SC up to maximum daily dose of 18 000 units or 100 units/kg twice daily if increased risk of haemorrhage.
Body
weight (kg)
|
Dose
(200 units/kg)
|
< 46
|
7500
once daily SC
|
46–56
|
10
000 once daily SC
|
57–68
|
12
500 once daily SC
|
69–82
|
15
00 once daily SC
|
>
83
|
18
000 once daily SC
|
• Unstable angina
Acute phase: 120 units/kg 12 hourly SC
Maximum dose: 10 000 units twice daily
Concomitant treatment with low-dose aspirin
Recommended treatment period up to 8 days
– Extended phase: men<70 kg, 5000 units once daily SC, >70 kg 7500 units once daily SC
– Women < 80 kg 5000 units once daily SC, >80 kg 7500 units once daily SC
Treatment should not be given for more than 45 days
Monitor: platelets
APTT monitoring is not usually required
In overdose, 100 units dalteparin is inhibited by 1 mg protamine
Adverse effects:
Subcutaneous haematoma at injection site
Bleeding at high doses, e.g., anti-Factor Xa levels greater than 1.5 iu/ml; however, at recommended doses bleeding rarely occurs
Transient increase in liver enzymes (ALT) but no clinical significance has been demonstrated
Rarely thrombocytopenia
Rarely hypoaldosteronism resulting in increased plasma potassium, particularly in chronic renal failure, diabetes mellitus or pre-existing metabolic acidosis
Organ failure:
Renal: for treatment doses where CC 30 ml/min avoid and replace with unfractionated heparin, as accumulation will occur, alternatively, use enoxaparin (p. 81) 1 mg/kg once daily. However for thromboprophylactic doses, it appears safe to use dalteparin 2500 units SC once daily.
Renal replacement therapy:
Treatment doses of LMWHs are generally avoided in renal replacement therapy, since anti-Xa monitoring is required to use safely.The use of unfractionated heparin is preferred.
0 comments:
Post a Comment