Heparin is a sulfated glycosaminoglycoside polymer of alternating chains of uronic acid and glucosamine, It can be:
- unfractionated (UFH), i.e. chains of various lengths with a molecular weight (MW) range of 5000–35 000 Da and mean MW of about 13 000–15 000 Da. There are several commercial preparations which are not equivalent (see box to right) .
- low molecular weight (LMWH), consisting of more uniform shorter chains. Each commercial preparation has slightly different properties. See low molecular weight heparins .
Acts via antithrombin.
- with UFH - Activated partial thromboplastin time
- with LMWH -anti-Xa activity- only necessary where reversal is needed.
- UFH for prophylaxis of VTE: 5000 units b.d./t.d.s.
- LMWH depends on product
- UFH as per Heparin sliding scale
UFH is not the same as LMWH clinically, and the greater convenience of LMWH and safety profile in routine practice has seen LMWH replace UFH for most indications. However UFH still has a place, but requires intensive monitoring at treatment rather than prophylaxis doses with individual dosage adjustment based on APPT. That clinical staff have become unskilled in giving it is a poor reason not to use it in circumstances where it may be the safest effective drug such as in bariatric (morbid obesity) patients.
- The main concern is risk of haemorrhage but it is important in prolonged use to monitor for heparin-induced thrombocytopenia.
- Natural protein antagonists are platelet factor 4 (PF4) and protamine. Both work best with UFH, indeed you need higher doses to reverse LMWH and although this is not seemingly clinically relevant, it is impossible to completely block LMWH in vitro.
Cautions and Interactions
Renal clearance predominates for LMWHs with increasing haemorrage risk in renal failure.
There is no evidence that UFH or LMWHs cross the placenta so they are presently the anticoagulants of choice in pregnancy.
- All heparins presently used in UK come from porcine sources.
- UFH heparin can be a sodium or calcium salt. They have different properties.
- Most LMWHs are sodium salts (fraxiparine -Nadroparin®),is a calcium salt).
- Low-molecular weight heparins have longer half-lives than UFH.
- In vivo there are differences in some indications, and dose must be right for indication.