Ancrod
Encyclopedia
Ancrod is a defibrinogenating agent derived from the venom
of the Malayan pit viper. Defibrinogenating blood produces an anticoagulant
effect. Ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trial
s. In January 2005, the U.S. Food and Drug Administration (FDA) granted 'fast-track status
' for investigating ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are being conducted.
and Austria
, until it was withdrawn in the 1980s. Arwin was a brand name of Knoll Pharma. Neurobiological Technologies, Inc., currently holds the worldwide rights to ancrod under the brand name Viprinex. Previously, the rights to Viprinex were held by Empire Pharmaceuticals, Inc., Abbott Laboratories
, and Knoll AG, developers of this investigational drug.
On 1 August 2005, Neurobiological Technologies, Inc. (NTI) agreed with Nordmark Arzneimittel GmbH & Co KG (Nordmark) and Baxter Pharmaceutical Solutions, LLC (Baxter) to manufacture, fill and package Viprinex for NTI's Phase III clinical trials in acute ischemic stroke. Nordmark will manufacture the biological active ingredient
, ancrod.
of the molecule
is an important factor. Glycosylation is remarkably homogenous with the major oligosaccharide
accounting for approximately 90% of the total sugar content. Some in vitro
reactions have been explored in detail (see ref. #2, www.blckwell-synergy). It was found that ancrod's actions are FAD
dependent and that the substance has interesting apoptotic properties (causing programmed cell death), which remain to be explored.
Ancrod is prepared from the crude venom
of the Malayan pit viper
(Agkistrodon rhodostoma, also termed Calloselasma rhodostoma) and belongs to the group of proteolytic enzyme
s. Ancrod may also be found in the venom of many venomous snakes (crotalids, elapids and viperids) in general, but the Malayan pit viper is most suitable due to a high concentration of ancrod in its venom. For its preparation a snake farm, very skilled and well trained staff (for milking the highly venomous snakes), and special production facilities are required to purify the enzyme.
The half-life
of ancrod is 3 to 5 hours and the drug is cleared from blood plasma
, mainly renally.
Due to its special mode of action (see below) and its price, Arwin was never been used as 'normal' anticoagulant such as heparin
, but only for the symptomatic treatment of moderate to severe forms of peripheral arterial circulatory disorders such as those resulting from years of heavy smoking and/or arteriosclerosis
.
The substance is intended for parenteral
, namely subcutaneous (s.c.) injection and intravenous (i.v.) infusion, and indirectly inhibits aggregation, adhesion
, and release of thrombocytes mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma fibrinogen
. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood viscosity
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 and perfusion
of the microcirculation
. Erythrocyte flexibility is not affected by normal doses of ancrod. The rheological 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 as cofactor
for the tPA
-induced plasminogen activation and an increased fibrinolysis
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 and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events.
These mechanisms also account for ancrod's activity in other diseases.
Effects on other clotting factors: Unlike thrombin
, ancrod does not directly activate Factor XIII
, nor does it produce platelet aggregation nor cause the release of ADP
, ATP
, potassium
, or serotonin
from platelets. Platelet counts and survival time remain normal during ancord therapy.
; central retinal and branch vein thrombosis; priapism
; pulmonary hypertension
of embolic origin; embolism
after insertion of prosthetic cardiac 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 and Raynaud's phenomenon
).
Ancrod has been shown to be useful for maintaining anticoagulation in the presence of Heparin-induced thrombocytopenia
(HIT) and thrombosis.
Currently, this drug is not approved nor available. It is being investigated in clinical trials for stroke.
, placebo-controlled German study of efficacy and safety of i.v. ancrod given within 6 hours after the onset of acute, ischemic stroke and continued for 5 days (called ESTAT study), the early findings for 800 patients were positive, but as the study was expanded to 1,600 patients, placebo was found to be more effective than ancrod and the study was abruptly terminated, mainly because the mortality rate
in the ancrod group was higher. The smaller American study 'Stroke Treatment with Ancrod Trial (STAT)' confirmed the negative outcome for ischemic stroke. In these studies, patients received a multi-day infusion of Viprinex designed to maintain patients’ fibrinogen level within a targeted range. Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be effective and safe.The ANCROD STROKE PROGRAM, was terminated in Jan 2009 for futility and NTI has terminated further development of the agent
Thrombocytopenia
as side effect has never been noticed with ancrod in contrast to heparin.
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...
of the Malayan pit viper. Defibrinogenating blood produces an anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
effect. Ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. In January 2005, the U.S. Food and Drug Administration (FDA) granted 'fast-track status
FDA Fast Track Development Program
The FDA Fast Track Development Program is a designation of the United States Food and Drug Administration that accelerates the approval of investigational new drugs undergoing clinical trials with the goal review time of 60 days...
' for investigating ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are being conducted.
Marketing history
Under the brand name Arwin, ancrod was marketed for several decades in GermanyGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
and Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
, until it was withdrawn in the 1980s. Arwin was a brand name of Knoll Pharma. Neurobiological Technologies, Inc., currently holds the worldwide rights to ancrod under the brand name Viprinex. Previously, the rights to Viprinex were held by Empire Pharmaceuticals, Inc., Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
, and Knoll AG, developers of this investigational drug.
On 1 August 2005, Neurobiological Technologies, Inc. (NTI) agreed with Nordmark Arzneimittel GmbH & Co KG (Nordmark) and Baxter Pharmaceutical Solutions, LLC (Baxter) to manufacture, fill and package Viprinex for NTI's Phase III clinical trials in acute ischemic stroke. Nordmark will manufacture the biological active ingredient
Active ingredient
An active ingredient is the substance of a pharmaceutical drug or a pharmaceutical ingredient and bulk active in medicine; in pesticide formulations active substance may be used. Some medications and pesticide products may contain more than one active ingredient...
, ancrod.
Chemistry and pharmacology
Ancrod has a triple mode of action. The exact structure and chemical data such as molecular weight are unknown, but it has been elaborated that the glycosylationGlycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
of the molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
is an important factor. Glycosylation is remarkably homogenous with the major oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
accounting for approximately 90% of the total sugar content. Some in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
reactions have been explored in detail (see ref. #2, www.blckwell-synergy). It was found that ancrod's actions are FAD
FAD
In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...
dependent and that the substance has interesting apoptotic properties (causing programmed cell death), which remain to be explored.
Ancrod is prepared from the crude venom
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...
of the Malayan pit viper
Viperidae
The Viperidae are a family of venomous snakes found all over the world, except in Antarctica, Australia, Ireland, Madagascar, Hawaii, various other isolated islands, and above the Arctic Circle. All have relatively long, hinged fangs that permit deep penetration and injection of venom. Four...
(Agkistrodon rhodostoma, also termed Calloselasma rhodostoma) and belongs to the group of proteolytic enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s. Ancrod may also be found in the venom of many venomous snakes (crotalids, elapids and viperids) in general, but the Malayan pit viper is most suitable due to a high concentration of ancrod in its venom. For its preparation a snake farm, very skilled and well trained staff (for milking the highly venomous snakes), and special production facilities are required to purify the enzyme.
The half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
of ancrod is 3 to 5 hours and the drug is cleared from blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, mainly renally.
Due to its special mode of action (see below) and its price, Arwin was never been used as 'normal' anticoagulant such as heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, but only for the symptomatic treatment of moderate to severe forms of peripheral arterial circulatory disorders such as those resulting from years of heavy smoking and/or arteriosclerosis
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
.
The substance is intended for parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
, namely subcutaneous (s.c.) injection and intravenous (i.v.) infusion, and indirectly inhibits aggregation, adhesion
Adhesion
Adhesion is any attraction process between dissimilar molecular species that can potentially bring them in close contact. By contrast, cohesion takes place between similar molecules....
, and release of thrombocytes mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood viscosity
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...
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
Amputation
Amputation is the removal of a body extremity by trauma, prolonged constriction, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on individuals as a preventative surgery for...
). 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 and perfusion
Perfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...
of the microcirculation
Microcirculation
The microcirculation is a term used to describe the small vessels in the vasculature which are embedded within organs and are responsible for the distribution of blood within tissues; as opposed to larger vessels in the macrocirculation which transport blood to and from the organs...
. Erythrocyte flexibility is not affected by normal doses of ancrod. The rheological 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 as cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
for the tPA
Tissue plasminogen activator
Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...
-induced plasminogen activation and an increased fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
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 and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events.
These mechanisms also account for ancrod's activity in other diseases.
Effects on other clotting factors: Unlike thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
, ancrod does not directly activate Factor XIII
Factor XIII
Factor XIII or fibrin stabilizing factor is an enzyme of the blood coagulation system that crosslinks fibrin.- Function :Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits...
, nor does it produce platelet aggregation nor cause the release of ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
, ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
, or serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
from platelets. Platelet counts and survival time remain normal during ancord therapy.
Historical
For the treatment of established deep vein thrombosisDeep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
; central retinal and branch vein thrombosis; priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...
; pulmonary hypertension
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
of embolic origin; embolism
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
after insertion of prosthetic cardiac 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
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
obliterans, thromboangiitis obliterans, diabetic microangiopathy and Raynaud's phenomenon
Raynaud's phenomenon
In medicine, Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas. This condition can also cause nails to become brittle with longitudinal ridges. Named for French physician Maurice Raynaud , the phenomenon is believed to be the...
).
Ancrod has been shown to be useful for maintaining anticoagulation in the presence of Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia is the development of thrombocytopenia , due to the administration of various forms of heparin, an anticoagulant...
(HIT) and thrombosis.
Currently, this drug is not approved nor available. It is being investigated in clinical trials for stroke.
Studies in early ischemic stroke
In a multicenter, parallel, group sequential, randomized, double-blindDouble-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, placebo-controlled German study of efficacy and safety of i.v. ancrod given within 6 hours after the onset of acute, ischemic stroke and continued for 5 days (called ESTAT study), the early findings for 800 patients were positive, but as the study was expanded to 1,600 patients, placebo was found to be more effective than ancrod and the study was abruptly terminated, mainly because the mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
in the ancrod group was higher. The smaller American study 'Stroke Treatment with Ancrod Trial (STAT)' confirmed the negative outcome for ischemic stroke. In these studies, patients received a multi-day infusion of Viprinex designed to maintain patients’ fibrinogen level within a targeted range. Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be effective and safe.The ANCROD STROKE PROGRAM, was terminated in Jan 2009 for futility and NTI has terminated further development of the agent
Contraindications and precautions
- Known bleeding disorders of any origin or any unexplained excessive bleedings in the past.
- Platelet counts of less than 100,000 (even if asymptomatic), exemption : HIT (Heparin- induced thrombocytopenia).
- Planned surgerySurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
or short before deliveryChildbirthChildbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
. - Active ulcerationsPeptic ulcerA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
of the GIT. - Any kind of malignantMalignantMalignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
disease. - Renal stones (increased likelihood of significant urological bleeding).
- Severe and uncontrolled arterial hypertension.
- Active pulmonary tuberculosis.
- Impaired fibrinolysisFibrinolysisFibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
. - Severe liver diseaseLiver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
. - Manifest or impending shock.
- I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing antibodies and therefore drug resistanceDrug resistanceDrug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
.
Pregnancy
Category X : Ancrod was not found to be teratogenic in animal studies, but some fetal deaths occurred as a result of placental 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.Side effects
- Hypersensitivity reactions : Local or generalized skin reactions (rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
and urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
); appearance of neutralizing antibodies to ancrod with partial or total loss of ancrod activity (drug resistance). - Sometimes pain at injection site (normally mild). This side effect may be, if necessary, treated with local or oral antihistaminic drugs (e.g., clemastineClemastineClemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines. Clemastine is also classified as an antipruritic...
, or diphenhydramineDiphenhydramineDiphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
). Bleeding at injection site, thrombophlebitisThrombophlebitisThrombophlebitis is phlebitis related to a thrombus . When it occurs repeatedly in different locations, it is known as "Thrombophlebitis migrans" or "migrating thrombophlebitis".-Signs and symptoms:...
at local veins, and (paradoxical) arterial thrombotic events. - Occasionally deposition of cleaved fibrinogen derivates in the spleen resulting in splenomegalySplenomegalySplenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
; rupture is possible, if the spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
is palpated too strongly (life-threatening bleeding and need of splenectomySplenectomyA splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
may result). - Specific side effects are local and systemic bleeding events. Local bleeding events may be treated with local pressure or surgical dressings, if necessary. Compared with other anticoagulants the risk of systemic bleeding is relatively low. If systemic bleeding is severe enough to warrant fast reversal of ancrod action, fibrinogen should be substituted (please refer to section 'special antidotes').
- Occasionally, increased headache has been found in patients with known migraineMigraineMigraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
. - Also, chills and feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
may occur infrequently.
Thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
as side effect has never been noticed with ancrod in contrast to heparin.