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| ECHA InfoCard | 100.029.927 |
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| Thrombin-like enzyme ancrod | |||||||
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| Identifiers | |||||||
| Organism | Calloselasma rhodostoma | ||||||
| Symbol | ? | ||||||
| UniProt | P26324 | ||||||
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| Thrombin-like enzyme ancrod-2 | |||||||
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| Identifiers | |||||||
| Organism | Calloselasma rhodostoma | ||||||
| Symbol | ? | ||||||
| UniProt | P47797 | ||||||
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Ancrod (current brand name:Viprinex) is adefibrinogenating agent derived from thevenom of theMalayan pit viper. Defibrinogenating blood produces ananticoagulant effect. Ancrod is not approved or marketed in any country. It is athrombin-likeserine protease.[1]
As of 2017 ancrod was not marketed for any medical use.[2]
Category X : Ancrod was not found to beteratogenic in animal studies, but somefetal deaths occurred as a result ofplacental hemorrhages in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg.
In clinical trials forischemic stroke, ancrod increased the risk ofintracerebral hemorrhage.[3]
Thrombocytopenia as side effect has never been noticed with ancrod in contrast to heparin.
It was not found to be of much use in the clinical trials.In vitro experiments show that it may actually clot blood.[4]
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Ancrod has a triple mode of action. It was found that ancrod's actions areFAD dependent and that the substance has interestingapoptotic properties (causing programmed cell death), which remain to be explored.
Thehalf-life of ancrod is 3 to 5 hours and the drug is cleared fromblood plasma, mainlyrenally.
Due to its special mode of action (see below) and its price, Arwin has never been used as 'normal' anticoagulant such asheparin, but only for the symptomatic treatment of moderate to severe forms of peripheral arterialcirculatory disorders such as those resulting from years of heavy smoking and/orarteriosclerosis.
The substance is intended forsubcutaneous injection andintravenous infusion, and indirectly inhibitsaggregation,adhesion, and release ofthrombocytes mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasmafibrinogen. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased bloodviscosity and thereby to a worsening of symptoms of the circulation disorder (more intense pain, decreased mobility of the limb and decreased temperature, need for partial or even total limb amputation). The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40% of the pretreatment levels. The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow andperfusion of themicrocirculation.Erythrocyte flexibility is not affected by normal doses of ancrod. Therheological changes are readily maintained and the viscosity approaches pretreatment values very slowly (within about 10 days) after stopping ancrod. One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts ascofactor for thetPA-inducedplasminogen activation and an increasedfibrinolysis results in return (profibrinolytic activity of ancrod).
Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical andergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events. These mechanisms also account for ancrod's activity in other diseases.
Effects on otherclotting factors: Unlikethrombin, ancrod does not directly activateFactor XIII, nor does it produceplatelet aggregation nor cause the release ofADP,ATP,potassium, orserotonin from platelets. Platelet counts and survival time remain normal during ancrod therapy.
Ancrod was originally isolated from thevenom of the Malayan pitviper (Calloselasma rhodostoma, formerlyAgkistrodon rhodostoma) and is aserine protease.[5] It is one of theVenombin A enzymes. Two genes encoding for such enzymes have been found in the viper genome.[6][7]
The form used in clinical trials was not made recombinantly, but was purified from harvested venom.[8][9]
Under the brand name Arwin, ancrod was marketed for several decades inGermany andAustria, until it was withdrawn in the 1980s. Arwin was a brand name ofKnoll Pharma.
In 2001 Knoll was acquired byAbbott Laboratories, and in 2002 Abbott licensed the rights to ancrod to Empire Pharmaceuticals.[10] In 2004 Empire was acquired byNeurobiological Technologies.[11] NTI also acquired a lot of unpurified venom in the acquisition, and had that purified for use in its clinical trials.[8][9]
The failure of ancrod in the 6-hour window for ischemic stroke trial in 2008 led to cuts in staff, an effort to sell off the company's assets, and finally to the dissolution of NTI in August 2009.[12][13]
Viprinex is not currently approved or available.
For the treatment of establisheddeep vein thrombosis; central retinal and branch vein thrombosis;priapism;pulmonary hypertension of embolic origin;embolism after insertion of prostheticcardiac valves; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.
For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g.,arteriosclerosis obliterans,thromboangiitis obliterans,diabetic microangiopathy andRaynaud's phenomenon).
Ancrod has been shown to be useful for maintaining anticoagulation in the presence ofHeparin-induced thrombocytopenia (HIT) and thrombosis.
A small study compared to ancrod toheparin in preventingthrombosis when given to people undergoing arterial graft surgery to treatperipheral arterial disease and found little difference between the two agents.[14]
Ancrod was intensively studied inischemic stroke, starting at least by the early 1990s.[15] An RCT called "STAT" was published in 2000; it included 500 subjects and ancrod or placebo was administered within three hours of the stroke. Ancrod showed modest benefits but a trend toward increasedintracranial haemorrhage.[5][16] A clinical trial published in 2006 found no benefit if ancrod was given within a wider 6 hour treatment window.[17] Another trial was launched to explore the 6 hour window, but it was halted early in 2008 when an independent review committee looked at the interim data and found no signal of benefit.[5][3][12]
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