phscism.jpg (3107 bytes)
feature.jpg (8474 bytes)

 

DANAPAROID (OrgaranŽ) for Heparin-Induced Thrombocytopenia

Karen Shalansky, Pharm.D.
February 1998 Drug & Therapeutics Newsletter
(C) 1998, CSU-Pharmaceutical Sceinces
Vancouver Hospital & Health Sciences Centre

Danaparoid sodium is an alternative anticoagulant in patients who develop heparin-induced thrombocytopenia (HIT) from heparin therapy. This drug is restricted to prescription by a hematologist.

Pharmacology

Danaparoid is a low molecular weight heparinoid derived from porcine gut mucosa. Its active components consist of heparan sulfate, dermatan sulfate and chondroitin sulfate. The major difference between danaparoid and other low molecular weight heparins (LMWH) is that danaparoid is devoid of heparin or heparin fragments. However, similar to LMWHs, it exerts its antithrombotic effect principally through anti-thrombin III-mediated inhibition of factor Xa and, to a much lesser extent, thrombin.1,2

Danaparoid is primarily eliminated via the kidneys. The elimination half-life based on anti-Xa activity ranges from 17-28 hours (mean 25 hours).

Comparison to Other Formulary Agents for Management of HIT

The incidence of HIT is approximately 1-3% with unfractionated heparin.1 Typical LMWHs (e.g. tinzaparin) exhibit a significant cross-reactivity with heparin-induced antibodies (incidence 79-100%) and thus have a high likelihood of causing platelet aggregation in patients with HIT.1-3 The cross-reactivity of danaparoid with heparin-induced antibodies is reported as less than 10% (range 0-20%).2,3

Ancrod represents a distinct anticoagulant that is derived from snake venom. Ancrod will not cross-react with heparin-induced antibodies, but neutralizing anti-ancrod antibodies can develop in patients who receive this agent for several weeks.4 Ancrod acts to reduce fibrinogen levels, thereby decreasing plasma viscosity. It does not inhibit thrombin, which may limit its use in some HIT patients, particularly those who have disseminated intravascular coagulation (DIC) or septicemia.4 As well, ancrod may not be useful in patients who are already hypofibrinogenemic.

Warfarin represents a third distinct anticoagulant. However, its onset of action is slow, taking up to 5 days for full anticoagulant effect.

Table 2. Comparison of Danaparoid and Ancrod

Drug Danaparoid Ancrod
Cross-reactivity with heparin-induced antibody (In vitro) < 10% (range 0-20%) 0%
Mechanism of action Anti-Xa:Anti-IIa

activity = 28:15

reduces fibrinogen levels and blood viscosity
Other considerations limited use if coexisting DIC or septicemia
Clotting Test

Assessment

none (does not affect global

clotting tests e.g. aPTT, INR, thrombin time)

fibrinogen levels
Cost/day (excludes

loading doses)

$115.00/day $243.00/day plus cost of

fibrinogen levels

Monitoring

As with all anticoagulants, the major side effect of danaparoid is bleeding; thrombocytopenia can rarely occur. Patients being treated for HIT should have daily CBC (with platelet counts) while receiving this drug.

Cross-reactivity of danaparoid with heparin-induced antibodies is less than 10% However, if after 48 hours following cessation of heparin and the initiation of danaparoid the platelets do not increase, the possibility of cross-reactivity should be considered and therapy switched to ancrod.

Dosing

Therapeutic Anticoagulation

Loading Dose: < 60 kg

60-75 kg

76-90 kg

> 90 kg

1500 units IV

2250 units IV

3000 units IV

3750 units IV

Maintenance Dose: 400 units/hr x 4 hrs, then 300 units/hr x 4 hrs, followed by 200 units/hr
DVT Prophylaxis

<= 90 kg

> 90 kg

750 units SC q12h

750 units SC q8h or

1250 units SC q12h

Table 3. Danaparoid Dosing

 

Conclusions

Danaparoid offers a less expensive, more convenient alternative to ancrod for anticoagulation in patients who develop HIT. Unlike ancrod, administration of danaparoid does not require routine laboratory test assessment for anticoagulation. It is important to continue to monitor daily platelet levels following cessation of heparin and initiation of danaparoid to ensure there is no cross-reactivity with heparin-induced antibodies.

References

1. Nurmohamed MT, ten Cate H, ten Cate JW. Low molecular weight heparin(oid)s. Drugs 1997;53:736-51.

2. Skoutakis VA. Danaparoid in the prevention of thromboembolic complications. Ann Pharmacol 1997;31:876-87.

3. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran. Thromb Hemost 1993;70:554-61.

4. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia: know what to do. Med NA 1995(Nov/Dec):942-9.

5. Bartle WR, Geerts W. Danaparoid and the prevention of thromboembolism. Can J Hosp Pharm 1997;50:55-60.