Page 2589 - Hematology_ Basic Principles and Practice ( PDFDrive )

2306 Part XIII Consultative Hematology

is limited by study design and that the safety concerns remain unre- Platelet gel combines microfibrillar collagen and thrombin with
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solved. Nonetheless, certain subgroups of patients, such as those patient-derived plasma that contains fibrinogen and platelets. Like
with platelet dysfunction, may derive benefit. 38,42-44 Because of the fibrin sealants, the product is applied using a dual-chamber syringe
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small but important risk for myocardial infarction, DDAVP should device. The presence of platelets improves clot strength and provides
be used with caution in any surgical patient with a history of or risk growth factors, but the need for centrifugation of patient blood and
factors for coronary artery disease. processing before use is a disadvantage. 46
Topical Hemostatic Agents Synthetic Agents

Topical hemostatic agents can be grouped into several categories: Cyanoacrylates are liquid monomers that rapidly polymerize in the
physical agents (bone wax, Ostene), absorbable agents (gelatin foams, presence of water and bind adjacent surfaces together. Octyl-2-cya-
oxidized cellulose, microfibrillar collagen), biologic agents (thrombin, noacrylate is useful for closing small wounds or incisions and provides
fibrin sealants, platelet gel), synthetic agents (polyethylene glycol good cosmetic results. 46
hydrogels, cyanoacrylates, glutaraldehyde cross-linked albumin), and Polyethylene glycol hydrogel can be sprayed onto tissues, where it
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hemostatic dressings. A thorough discussion of the currently avail- rapidly forms a cross-linked polymer matrix and serves as a sealant
able products, including mechanisms of action, specific advantages that inhibits cell ingrowth and adhesion formation. It is useful for
and disadvantages, and recommendations for their use is provided in preventing pericardial adhesions and as a mechanical sealant for
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a recent comprehensive review. A brief overview of the different vascular reconstructions in situations where swelling and expansion
types of topical hemostatic agents follows. are not a concern. 46
Glutaraldehyde cross-linked bovine albumin is primarily used to
seal sutures or staple lines in complex cardiovascular procedures.
Physical Agents However, because it can restrict tissue growth, it should not be used
circumferentially around developing structures, particularly in
Bone wax and alkylene oxide copolymers (Ostene) control hemor- children. 46
rhage by occluding bleeding channels on cut bone surfaces, and are
often used in cardiac and orthopedic surgery. Ostene is preferred
because it does not impede bone growth and is eventually absorbed. Hemostatic Dressings
Both can increase the risk for local infection. 46
Progress in the field of topical hemostatic agents over the last decade
has expanded into the development of hemostatic dressings. Several
Absorbable Agents products containing combinations of gauze and lyophilized fibrino-
gen and thrombin, chitin, and chitosan (polysaccharides found in
Gelatin foams are derived from animal products and provide a physical arthropod skeletons and produced by fermenting algae), and mineral
matrix upon which clotting occurs. These products expand to double zeolite are available. In general, the use of hemostatic dressings is still
their volume, an attractive feature for use in penetrating wounds, but under investigation, primarily by the military and emergency first
potentially problematic if used near nerves or in confined spaces. 46 responders. 46
Oxidized cellulose is derived from wood pulp. It provides a
physical matrix for initiation of clotting and has excellent handling
characteristics. By lowering surrounding pH, oxidized cellulose exerts Antifibrinolytics
an antimicrobial effect, but this property not only limits its use with
biologic agents such as thrombin that are pH sensitive, but also can Antifibrinolytic agents include the synthetic lysine analogues
contribute to local inflammation. 46 6-aminohexanoic acid (aminocaproic acid) and 4-(aminomethyl)
Microfibrillar collagen is derived from bovine components. It con- cyclohexanecarboxylic acid (tranexamic acid), and the serine protease
tributes to hemostasis by promoting platelet adherence and activation inhibitor, aprotinin. Although both types of antifibrinolytic agents
and is effective in controlling wide-spread parenchymal bleeding. have been used in managing surgical bleeding, the lysine analogues
Consequently, it can be useful even in the face of heparin therapy, are available in oral forms that facilitate their use in other clinical
although it is less effective in the setting of thrombocytopenia. 46 situations as well.

Biologic Agents Aminocaproic Acid and Tranexamic Acid
Thrombin derived from bovine plasma was used for more than 40 years Both aminocaproic acid and tranexamic acid bind reversibly to the
as a topical hemostatic agent in surgical patients. However, bovine lysine binding sites on plasminogen, thereby attenuating its capacity
thrombin can trigger the formation of antibodies that cross-react with to bind to fibrin, which is essential for its activation by plasminogen
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human thrombin, leading to hemorrhagic complications. 47-49 Because activators. Although tranexamic acid is approximately 10 times
of these issues, plasma-derived and recombinant forms of human more potent than aminocaproic acid and has a longer half-life, both
thrombin were developed. A phase III randomized, double-blind trial drugs have similar hemostatic effects. 52
found that the efficacy and safety of recombinant human thrombin Because the oral form of tranexamic acid was not commercially
and bovine thrombin were comparable, but there were fewer immu- available in the United States for a number of years, aminocaproic
nologic complications with recombinant human thrombin. 50 acid became the lysine derivative of choice for oral delivery. Amino-
Fibrin sealants are topical hemostatic agents composed of purified caproic acid is commonly used to treat mucosal hemorrhage (menor-
virally inactivated human fibrinogen and human thrombin. Some rhagia, epistaxis, dental bleeding) in patients with congenital
products also add human factor XIII to induce fibrin crosslinking and coagulopathies and is also effective for prevention of oral bleeding in
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antifibrinolytic agents to prevent clot breakdown. The components those who require dental work while receiving long-term oral antico-
of fibrin sealants are supplied in separate chambers of a dual-syringe agulant therapy.
delivery device that combines them at the time of administration. Although aminocaproic acid is sometimes used to treat bleeding
The final steps of the coagulation cascade are reproduced, resulting in patients with thrombocytopenia, randomized controlled trials are
in formation of a stable fibrin clot. These products are particularly lacking. The use of antifibrinolytic drugs in patients with gastro-
effective for controlling oozing from raw surfaces. 46 intestinal bleeding is reasonable given the high concentration of