No results found.
Amanda A. Cavanagh, DVM, DACVECC, is an assistant professor of small animal emergency and critical care section head of the urgent care service at Colorado State University. She earned her DVM from and completed a residency at North Carolina State University. Dr. Cavanagh has a special interest in traumatology, toxicology, fluid resuscitation, and point of care ultrasonography.
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The following case pertains to questions 1 through 3.
A 10-year-old, 66-lb (30-kg) spayed greyhound is presented for acute non-weight–bearing lameness of the left thoracic limb that developed after chasing a rabbit. Radiographs reveal a lytic lesion of the distal humerus consistent with osteosarcoma and an associated pathologic fracture. Amputation of the thoracic limb is scheduled for the following day.
Which of the following conditions can result in coagulation abnormalities in greyhounds?
Hemophilia A
Hyperfibrinolysis
Von Willebrand disease
Thrombocytopenia with macrothrombocytosis
The correct answer is B. Hyperfibrinolysis (ie, accelerated clot breakdown) can cause delayed postoperative bleeding (ie, hemorrhage beginning 36-48 hours postoperatively) in greyhounds.1 Bleeding is characterized by cutaneous bruising that extends from the surgical incision toward the periphery. In a study, 26% of greyhounds experienced delayed postoperative hemorrhage following neutering or ovariohysterectomy.1 No mucosal bleeding or bleeding away from the surgical site occurred.1 In another study, 28% of greyhounds experienced delayed hemorrhage following limb amputation for appendicular osteosarcoma.2 Dogs that experienced delayed bleeding had normal primary and/or secondary hemostasis, and none of the study dogs experienced intraoperative or immediate postoperative bleeding.1 Hemorrhage appears to be self-limiting, although RBC and plasma transfusions may be required in some dogs to treat marked hemorrhage.
Hemophilia A is an X-linked, recessive, inherited coagulation disorder caused by a deficiency of factor 8. Because of hemophilia A’s X-linked inheritance, male dogs are more commonly affected than female dogs. In a study, most affected dogs were crossbreeds, German shepherd dogs, or Labrador retrievers.3 The most common initial signs of hemophilia A include spontaneous bruising or hematoma formation, excessive bleeding after minor trauma or during surgical procedures, gingival bleeding during teething and loss of deciduous teeth, and spontaneous bleeding into a body cavity.3
Von Willebrand disease can occur due to a deficiency or abnormality in the von Willebrand factor, which is stored in platelets and endothelial cells and is essential for platelet adhesion and aggregation at the site of endothelial injury. Many dog breeds are affected by this inherited disorder. The severity of bleeding is variable. Severely affected dogs may have spontaneous mucosal bleeding, whereas less severely affected dogs may only display abnormal bleeding during trauma or surgery.4
Clinically inapparent, idiopathic thrombocytopenia with macrothrombocytosis is an autosomal recessive trait that affects 50% of Cavalier King Charles spaniels.5 Dogs are not clinically affected by this condition, and those with this condition do not have an increased risk for hemorrhage.5,6
The correct answer is B. Hyperfibrinolysis (ie, accelerated clot breakdown) can cause delayed postoperative bleeding (ie, hemorrhage beginning 36-48 hours postoperatively) in greyhounds.1 Bleeding is characterized by cutaneous bruising that extends from the surgical incision toward the periphery. In a study, 26% of greyhounds experienced delayed postoperative hemorrhage following neutering or ovariohysterectomy.1 No mucosal bleeding or bleeding away from the surgical site occurred.1 In another study, 28% of greyhounds experienced delayed hemorrhage following limb amputation for appendicular osteosarcoma.2 Dogs that experienced delayed bleeding had normal primary and/or secondary hemostasis, and none of the study dogs experienced intraoperative or immediate postoperative bleeding.1 Hemorrhage appears to be self-limiting, although RBC and plasma transfusions may be required in some dogs to treat marked hemorrhage.
Hemophilia A is an X-linked, recessive, inherited coagulation disorder caused by a deficiency of factor 8. Because of hemophilia A’s X-linked inheritance, male dogs are more commonly affected than female dogs. In a study, most affected dogs were crossbreeds, German shepherd dogs, or Labrador retrievers.3 The most common initial signs of hemophilia A include spontaneous bruising or hematoma formation, excessive bleeding after minor trauma or during surgical procedures, gingival bleeding during teething and loss of deciduous teeth, and spontaneous bleeding into a body cavity.3
Von Willebrand disease can occur due to a deficiency or abnormality in the von Willebrand factor, which is stored in platelets and endothelial cells and is essential for platelet adhesion and aggregation at the site of endothelial injury. Many dog breeds are affected by this inherited disorder. The severity of bleeding is variable. Severely affected dogs may have spontaneous mucosal bleeding, whereas less severely affected dogs may only display abnormal bleeding during trauma or surgery.4
Clinically inapparent, idiopathic thrombocytopenia with macrothrombocytosis is an autosomal recessive trait that affects 50% of Cavalier King Charles spaniels.5 Dogs are not clinically affected by this condition, and those with this condition do not have an increased risk for hemorrhage.5,6
The correct answer is B. Hyperfibrinolysis (ie, accelerated clot breakdown) can cause delayed postoperative bleeding (ie, hemorrhage beginning 36-48 hours postoperatively) in greyhounds.1 Bleeding is characterized by cutaneous bruising that extends from the surgical incision toward the periphery. In a study, 26% of greyhounds experienced delayed postoperative hemorrhage following neutering or ovariohysterectomy.1 No mucosal bleeding or bleeding away from the surgical site occurred.1 In another study, 28% of greyhounds experienced delayed hemorrhage following limb amputation for appendicular osteosarcoma.2 Dogs that experienced delayed bleeding had normal primary and/or secondary hemostasis, and none of the study dogs experienced intraoperative or immediate postoperative bleeding.1 Hemorrhage appears to be self-limiting, although RBC and plasma transfusions may be required in some dogs to treat marked hemorrhage.
Hemophilia A is an X-linked, recessive, inherited coagulation disorder caused by a deficiency of factor 8. Because of hemophilia A’s X-linked inheritance, male dogs are more commonly affected than female dogs. In a study, most affected dogs were crossbreeds, German shepherd dogs, or Labrador retrievers.3 The most common initial signs of hemophilia A include spontaneous bruising or hematoma formation, excessive bleeding after minor trauma or during surgical procedures, gingival bleeding during teething and loss of deciduous teeth, and spontaneous bleeding into a body cavity.3
Von Willebrand disease can occur due to a deficiency or abnormality in the von Willebrand factor, which is stored in platelets and endothelial cells and is essential for platelet adhesion and aggregation at the site of endothelial injury. Many dog breeds are affected by this inherited disorder. The severity of bleeding is variable. Severely affected dogs may have spontaneous mucosal bleeding, whereas less severely affected dogs may only display abnormal bleeding during trauma or surgery.4
Clinically inapparent, idiopathic thrombocytopenia with macrothrombocytosis is an autosomal recessive trait that affects 50% of Cavalier King Charles spaniels.5 Dogs are not clinically affected by this condition, and those with this condition do not have an increased risk for hemorrhage.5,6
The correct answer is B. Hyperfibrinolysis (ie, accelerated clot breakdown) can cause delayed postoperative bleeding (ie, hemorrhage beginning 36-48 hours postoperatively) in greyhounds.1 Bleeding is characterized by cutaneous bruising that extends from the surgical incision toward the periphery. In a study, 26% of greyhounds experienced delayed postoperative hemorrhage following neutering or ovariohysterectomy.1 No mucosal bleeding or bleeding away from the surgical site occurred.1 In another study, 28% of greyhounds experienced delayed hemorrhage following limb amputation for appendicular osteosarcoma.2 Dogs that experienced delayed bleeding had normal primary and/or secondary hemostasis, and none of the study dogs experienced intraoperative or immediate postoperative bleeding.1 Hemorrhage appears to be self-limiting, although RBC and plasma transfusions may be required in some dogs to treat marked hemorrhage.
Hemophilia A is an X-linked, recessive, inherited coagulation disorder caused by a deficiency of factor 8. Because of hemophilia A’s X-linked inheritance, male dogs are more commonly affected than female dogs. In a study, most affected dogs were crossbreeds, German shepherd dogs, or Labrador retrievers.3 The most common initial signs of hemophilia A include spontaneous bruising or hematoma formation, excessive bleeding after minor trauma or during surgical procedures, gingival bleeding during teething and loss of deciduous teeth, and spontaneous bleeding into a body cavity.3
Von Willebrand disease can occur due to a deficiency or abnormality in the von Willebrand factor, which is stored in platelets and endothelial cells and is essential for platelet adhesion and aggregation at the site of endothelial injury. Many dog breeds are affected by this inherited disorder. The severity of bleeding is variable. Severely affected dogs may have spontaneous mucosal bleeding, whereas less severely affected dogs may only display abnormal bleeding during trauma or surgery.4
Clinically inapparent, idiopathic thrombocytopenia with macrothrombocytosis is an autosomal recessive trait that affects 50% of Cavalier King Charles spaniels.5 Dogs are not clinically affected by this condition, and those with this condition do not have an increased risk for hemorrhage.5,6
What drug has been proven to be effective in the prevention and treatment of delayed postoperative hemorrhage in greyhounds?
Unfractionated heparin
Apixaban
Tissue plasminogen activator
Aminocaproic acid
The correct answer is D. Aminocaproic acid has been shown to significantly decrease the prevalence of postoperative bleeding by increasing clot strength and decreasing clot lysis.2 Aminocaproic acid prevents activation of plasminogen to plasmin, thereby preventing fibrinolysis (Figure 1); stabilizes clots; and prevents hemorrhage.7 In a study of greyhounds undergoing gonadectomy, incidence of hemorrhage was 30% in the placebo group and 10% in the aminocaproic acid-treated group.8
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
Unfractionated heparin is a parenteral anticoagulant used to prevent macrovascular thromboembolism in predisposed patients (eg, those with immune-mediated hemolytic anemia). Heparin does not lyse pre-existing clots but can prevent expansion of these clots.9
Apixaban is an oral anticoagulant that can help prevent clotting by inhibiting activated factor 10. Inhibition of activated factor 10 prevents activation of prothrombin to thrombin, which is necessary for the conversion of fibrinogen to fibrin.10
Tissue plasminogen activator (tPA; Figure 2) is a parenteral drug used to lyse clots and converts plasminogen to plasmin, which induces fibrinolysis.10
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
The correct answer is D. Aminocaproic acid has been shown to significantly decrease the prevalence of postoperative bleeding by increasing clot strength and decreasing clot lysis.2 Aminocaproic acid prevents activation of plasminogen to plasmin, thereby preventing fibrinolysis (Figure 1); stabilizes clots; and prevents hemorrhage.7 In a study of greyhounds undergoing gonadectomy, incidence of hemorrhage was 30% in the placebo group and 10% in the aminocaproic acid-treated group.8
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
Unfractionated heparin is a parenteral anticoagulant used to prevent macrovascular thromboembolism in predisposed patients (eg, those with immune-mediated hemolytic anemia). Heparin does not lyse pre-existing clots but can prevent expansion of these clots.9
Apixaban is an oral anticoagulant that can help prevent clotting by inhibiting activated factor 10. Inhibition of activated factor 10 prevents activation of prothrombin to thrombin, which is necessary for the conversion of fibrinogen to fibrin.10
Tissue plasminogen activator (tPA; Figure 2) is a parenteral drug used to lyse clots and converts plasminogen to plasmin, which induces fibrinolysis.10
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
The correct answer is D. Aminocaproic acid has been shown to significantly decrease the prevalence of postoperative bleeding by increasing clot strength and decreasing clot lysis.2 Aminocaproic acid prevents activation of plasminogen to plasmin, thereby preventing fibrinolysis (Figure 1); stabilizes clots; and prevents hemorrhage.7 In a study of greyhounds undergoing gonadectomy, incidence of hemorrhage was 30% in the placebo group and 10% in the aminocaproic acid-treated group.8
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
Unfractionated heparin is a parenteral anticoagulant used to prevent macrovascular thromboembolism in predisposed patients (eg, those with immune-mediated hemolytic anemia). Heparin does not lyse pre-existing clots but can prevent expansion of these clots.9
Apixaban is an oral anticoagulant that can help prevent clotting by inhibiting activated factor 10. Inhibition of activated factor 10 prevents activation of prothrombin to thrombin, which is necessary for the conversion of fibrinogen to fibrin.10
Tissue plasminogen activator (tPA; Figure 2) is a parenteral drug used to lyse clots and converts plasminogen to plasmin, which induces fibrinolysis.10
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
The correct answer is D. Aminocaproic acid has been shown to significantly decrease the prevalence of postoperative bleeding by increasing clot strength and decreasing clot lysis.2 Aminocaproic acid prevents activation of plasminogen to plasmin, thereby preventing fibrinolysis (Figure 1); stabilizes clots; and prevents hemorrhage.7 In a study of greyhounds undergoing gonadectomy, incidence of hemorrhage was 30% in the placebo group and 10% in the aminocaproic acid-treated group.8
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
FIGURE 1 Tranexamic acid and aminocaproic acid are fibrinolytic inhibitors with similar mechanisms of action. These drugs are lysine analogs that prevent activation of plasminogen to plasmin by blocking the C-terminal lysine binding site of plasminogen, thereby preventing fibrinolysis.
Unfractionated heparin is a parenteral anticoagulant used to prevent macrovascular thromboembolism in predisposed patients (eg, those with immune-mediated hemolytic anemia). Heparin does not lyse pre-existing clots but can prevent expansion of these clots.9
Apixaban is an oral anticoagulant that can help prevent clotting by inhibiting activated factor 10. Inhibition of activated factor 10 prevents activation of prothrombin to thrombin, which is necessary for the conversion of fibrinogen to fibrin.10
Tissue plasminogen activator (tPA; Figure 2) is a parenteral drug used to lyse clots and converts plasminogen to plasmin, which induces fibrinolysis.10
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
FIGURE 2 tPA binds to plasminogen, inducing a conformational change that converts plasminogen to plasmin. Plasmin proteolyses fibrin into fibrin degradation products (FDP), thus breaking down the clot.
What coagulation test measures the rate of fibrinolysis?
Thromboelastography
Activated clotting time
Buccal mucosal bleeding time
D-dimers
The correct answer is A. Thromboelastography is an in vitro test of the global coagulation process that measures the rate of clot formation, maximum clot strength, and rate of fibrinolysis.11
Activated clotting time (ACT) measures the intrinsic and common pathways of coagulation. Prolonged ACT is the only relevant finding and is suggestive of hypocoagulability. Shortened ACT cannot be interpreted as hypercoagulability. Prolonged ACT can indicate severe inherited or acquired clotting factor deficiencies. Thrombocytopenia can result in mildly prolonged ACT.
Buccal mucosal bleeding time is an in vivo test of primary hemostasis and is prolonged with severe platelet dysfunction or von Willebrand disease.12
D-dimers are degradation products of a cross-linked fibrin clot and increase with clot formation and degradation. D-dimers do not reflect the rate of fibrinolysis.13
The correct answer is A. Thromboelastography is an in vitro test of the global coagulation process that measures the rate of clot formation, maximum clot strength, and rate of fibrinolysis.11
Activated clotting time (ACT) measures the intrinsic and common pathways of coagulation. Prolonged ACT is the only relevant finding and is suggestive of hypocoagulability. Shortened ACT cannot be interpreted as hypercoagulability. Prolonged ACT can indicate severe inherited or acquired clotting factor deficiencies. Thrombocytopenia can result in mildly prolonged ACT.
Buccal mucosal bleeding time is an in vivo test of primary hemostasis and is prolonged with severe platelet dysfunction or von Willebrand disease.12
D-dimers are degradation products of a cross-linked fibrin clot and increase with clot formation and degradation. D-dimers do not reflect the rate of fibrinolysis.13
The correct answer is A. Thromboelastography is an in vitro test of the global coagulation process that measures the rate of clot formation, maximum clot strength, and rate of fibrinolysis.11
Activated clotting time (ACT) measures the intrinsic and common pathways of coagulation. Prolonged ACT is the only relevant finding and is suggestive of hypocoagulability. Shortened ACT cannot be interpreted as hypercoagulability. Prolonged ACT can indicate severe inherited or acquired clotting factor deficiencies. Thrombocytopenia can result in mildly prolonged ACT.
Buccal mucosal bleeding time is an in vivo test of primary hemostasis and is prolonged with severe platelet dysfunction or von Willebrand disease.12
D-dimers are degradation products of a cross-linked fibrin clot and increase with clot formation and degradation. D-dimers do not reflect the rate of fibrinolysis.13
The correct answer is A. Thromboelastography is an in vitro test of the global coagulation process that measures the rate of clot formation, maximum clot strength, and rate of fibrinolysis.11
Activated clotting time (ACT) measures the intrinsic and common pathways of coagulation. Prolonged ACT is the only relevant finding and is suggestive of hypocoagulability. Shortened ACT cannot be interpreted as hypercoagulability. Prolonged ACT can indicate severe inherited or acquired clotting factor deficiencies. Thrombocytopenia can result in mildly prolonged ACT.
Buccal mucosal bleeding time is an in vivo test of primary hemostasis and is prolonged with severe platelet dysfunction or von Willebrand disease.12
D-dimers are degradation products of a cross-linked fibrin clot and increase with clot formation and degradation. D-dimers do not reflect the rate of fibrinolysis.13
The following case pertains to questions 4 and 5.
A 3-year-old neutered male German shepherd dog is presented 30 minutes after being hit by a truck. He is laterally recumbent and has a heart rate of 220 bpm, weak femoral pulses, and pale mucous membranes. Blood pressure is 60 mm Hg (Doppler). Initial abdominal- and thoracic-focused assessment with sonography in trauma scans reveal mild thoracic effusion and moderate peritoneal effusion. Abdominocentesis reveals hemorrhagic effusion. Both prothrombin time and activated partial thromboplastin time are moderately prolonged. Bolus fluid therapy is initiated to correct hypovolemic shock, and aminocaproic acid (50 mg/kg IV) is administered.14
Aminocaproic acid can be helpful in the treatment of which suspected condition in this patient?
Thromboembolic disease
Acute traumatic coagulopathy
Hyperfibrinogenemia
Pain
The correct answer is B. Acute traumatic coagulopathy (ATC) is a syndrome that can occur immediately after trauma and is characterized by consumptive coagulopathy due to massive thrombin generation followed by rapid clot breakdown. Severe tissue injury, shock, tissue hypoperfusion, and catecholamines stimulate pathologic systemic coagulation. ATC occurs independent of fluids or drugs used to resuscitate trauma victims. The degree of coagulopathy is correlated with the severity of injury and shock.15,16 ATC is an independent risk factor for death in humans.17 In a retrospective study, 15% of dogs suffering severe blunt or penetrating trauma displayed coagulation abnormalities consistent with ATC on presentation.18
Aminocaproic acid can help reverse the pathology associated with ATC.19 Aminocaproic acid has no analgesic properties, enhances clot strength, and inhibits clot lysis; thus, its use is contraindicated in the treatment of thromboembolic disease.7 Fibrinogen is an acute phase reactant protein that increases in response to inflammatory cytokines.10 Hyperfibrinogenemia does not result in rapid clot breakdown or hemorrhage; therefore, aminocaproic acid is not warranted.
The correct answer is B. Acute traumatic coagulopathy (ATC) is a syndrome that can occur immediately after trauma and is characterized by consumptive coagulopathy due to massive thrombin generation followed by rapid clot breakdown. Severe tissue injury, shock, tissue hypoperfusion, and catecholamines stimulate pathologic systemic coagulation. ATC occurs independent of fluids or drugs used to resuscitate trauma victims. The degree of coagulopathy is correlated with the severity of injury and shock.15,16 ATC is an independent risk factor for death in humans.17 In a retrospective study, 15% of dogs suffering severe blunt or penetrating trauma displayed coagulation abnormalities consistent with ATC on presentation.18
Aminocaproic acid can help reverse the pathology associated with ATC.19 Aminocaproic acid has no analgesic properties, enhances clot strength, and inhibits clot lysis; thus, its use is contraindicated in the treatment of thromboembolic disease.7 Fibrinogen is an acute phase reactant protein that increases in response to inflammatory cytokines.10 Hyperfibrinogenemia does not result in rapid clot breakdown or hemorrhage; therefore, aminocaproic acid is not warranted.
The correct answer is B. Acute traumatic coagulopathy (ATC) is a syndrome that can occur immediately after trauma and is characterized by consumptive coagulopathy due to massive thrombin generation followed by rapid clot breakdown. Severe tissue injury, shock, tissue hypoperfusion, and catecholamines stimulate pathologic systemic coagulation. ATC occurs independent of fluids or drugs used to resuscitate trauma victims. The degree of coagulopathy is correlated with the severity of injury and shock.15,16 ATC is an independent risk factor for death in humans.17 In a retrospective study, 15% of dogs suffering severe blunt or penetrating trauma displayed coagulation abnormalities consistent with ATC on presentation.18
Aminocaproic acid can help reverse the pathology associated with ATC.19 Aminocaproic acid has no analgesic properties, enhances clot strength, and inhibits clot lysis; thus, its use is contraindicated in the treatment of thromboembolic disease.7 Fibrinogen is an acute phase reactant protein that increases in response to inflammatory cytokines.10 Hyperfibrinogenemia does not result in rapid clot breakdown or hemorrhage; therefore, aminocaproic acid is not warranted.
The correct answer is B. Acute traumatic coagulopathy (ATC) is a syndrome that can occur immediately after trauma and is characterized by consumptive coagulopathy due to massive thrombin generation followed by rapid clot breakdown. Severe tissue injury, shock, tissue hypoperfusion, and catecholamines stimulate pathologic systemic coagulation. ATC occurs independent of fluids or drugs used to resuscitate trauma victims. The degree of coagulopathy is correlated with the severity of injury and shock.15,16 ATC is an independent risk factor for death in humans.17 In a retrospective study, 15% of dogs suffering severe blunt or penetrating trauma displayed coagulation abnormalities consistent with ATC on presentation.18
Aminocaproic acid can help reverse the pathology associated with ATC.19 Aminocaproic acid has no analgesic properties, enhances clot strength, and inhibits clot lysis; thus, its use is contraindicated in the treatment of thromboembolic disease.7 Fibrinogen is an acute phase reactant protein that increases in response to inflammatory cytokines.10 Hyperfibrinogenemia does not result in rapid clot breakdown or hemorrhage; therefore, aminocaproic acid is not warranted.
Aminocaproic acid treats acute traumatic coagulopathy (ATC) through which of the following methods?
Inhibition of platelet activation
Stimulation of tissue factor expression
Inhibition of fibrin breakdown
Activation of plasminogen to plasmin
The correct answer is C. Aminocaproic acid prevents fibrin and clot breakdown and maintains clot strength by preventing conversion of plasminogen to plasmin, which subsequently breaks down the fibrin clot.19 Hyperfibrinolysis plays an integral role in ATC; early treatment with an antifibrinolytic is key to successful posttraumatic resuscitation. In humans, administration of aminocaproic acid within 3 hours of trauma reduces the risk for death due to bleeding without increasing the risk for thrombotic events.20 In a study in humans, administration of aminocaproic acid >3 hours posttrauma increased the risk for death from bleeding. No studies have been conducted in veterinary patients specifically evaluating this drug in the treatment of ATC, although results from studies in humans are promising.
Platelet-inhibiting drugs include aspirin and clopidogrel. Aminocaproic acid does not have any effects on platelet function.7
Tissue factor is present in the subendothelial tissue and endothelial, inflammatory, and neoplastic cells. Tissue factor expression is stimulated by blood vessel damage or inflammatory cytokines. Tissue factor expression leads to the generation of thrombin and simulates formation of a fibrin clot.10 Aminocaproic acid has no know effect on tissue factor expression and does not affect clot formation or strength through this pathway.
Tissue plasminogen activator activates plasminogen to plasmin, which breaks down fibrin clots into D-dimers and fibrin degradation products. Tissue plasminogen activator initiates the fibrinolytic process, whereas aminocaproic acid inhibits the fibrinolytic process.10
The correct answer is C. Aminocaproic acid prevents fibrin and clot breakdown and maintains clot strength by preventing conversion of plasminogen to plasmin, which subsequently breaks down the fibrin clot.19 Hyperfibrinolysis plays an integral role in ATC; early treatment with an antifibrinolytic is key to successful posttraumatic resuscitation. In humans, administration of aminocaproic acid within 3 hours of trauma reduces the risk for death due to bleeding without increasing the risk for thrombotic events.20 In a study in humans, administration of aminocaproic acid >3 hours posttrauma increased the risk for death from bleeding. No studies have been conducted in veterinary patients specifically evaluating this drug in the treatment of ATC, although results from studies in humans are promising.
Platelet-inhibiting drugs include aspirin and clopidogrel. Aminocaproic acid does not have any effects on platelet function.7
Tissue factor is present in the subendothelial tissue and endothelial, inflammatory, and neoplastic cells. Tissue factor expression is stimulated by blood vessel damage or inflammatory cytokines. Tissue factor expression leads to the generation of thrombin and simulates formation of a fibrin clot.10 Aminocaproic acid has no know effect on tissue factor expression and does not affect clot formation or strength through this pathway.
Tissue plasminogen activator activates plasminogen to plasmin, which breaks down fibrin clots into D-dimers and fibrin degradation products. Tissue plasminogen activator initiates the fibrinolytic process, whereas aminocaproic acid inhibits the fibrinolytic process.10
The correct answer is C. Aminocaproic acid prevents fibrin and clot breakdown and maintains clot strength by preventing conversion of plasminogen to plasmin, which subsequently breaks down the fibrin clot.19 Hyperfibrinolysis plays an integral role in ATC; early treatment with an antifibrinolytic is key to successful posttraumatic resuscitation. In humans, administration of aminocaproic acid within 3 hours of trauma reduces the risk for death due to bleeding without increasing the risk for thrombotic events.20 In a study in humans, administration of aminocaproic acid >3 hours posttrauma increased the risk for death from bleeding. No studies have been conducted in veterinary patients specifically evaluating this drug in the treatment of ATC, although results from studies in humans are promising.
Platelet-inhibiting drugs include aspirin and clopidogrel. Aminocaproic acid does not have any effects on platelet function.7
Tissue factor is present in the subendothelial tissue and endothelial, inflammatory, and neoplastic cells. Tissue factor expression is stimulated by blood vessel damage or inflammatory cytokines. Tissue factor expression leads to the generation of thrombin and simulates formation of a fibrin clot.10 Aminocaproic acid has no know effect on tissue factor expression and does not affect clot formation or strength through this pathway.
Tissue plasminogen activator activates plasminogen to plasmin, which breaks down fibrin clots into D-dimers and fibrin degradation products. Tissue plasminogen activator initiates the fibrinolytic process, whereas aminocaproic acid inhibits the fibrinolytic process.10
The correct answer is C. Aminocaproic acid prevents fibrin and clot breakdown and maintains clot strength by preventing conversion of plasminogen to plasmin, which subsequently breaks down the fibrin clot.19 Hyperfibrinolysis plays an integral role in ATC; early treatment with an antifibrinolytic is key to successful posttraumatic resuscitation. In humans, administration of aminocaproic acid within 3 hours of trauma reduces the risk for death due to bleeding without increasing the risk for thrombotic events.20 In a study in humans, administration of aminocaproic acid >3 hours posttrauma increased the risk for death from bleeding. No studies have been conducted in veterinary patients specifically evaluating this drug in the treatment of ATC, although results from studies in humans are promising.
Platelet-inhibiting drugs include aspirin and clopidogrel. Aminocaproic acid does not have any effects on platelet function.7
Tissue factor is present in the subendothelial tissue and endothelial, inflammatory, and neoplastic cells. Tissue factor expression is stimulated by blood vessel damage or inflammatory cytokines. Tissue factor expression leads to the generation of thrombin and simulates formation of a fibrin clot.10 Aminocaproic acid has no know effect on tissue factor expression and does not affect clot formation or strength through this pathway.
Tissue plasminogen activator activates plasminogen to plasmin, which breaks down fibrin clots into D-dimers and fibrin degradation products. Tissue plasminogen activator initiates the fibrinolytic process, whereas aminocaproic acid inhibits the fibrinolytic process.10
Which of the following drugs is also a lysine analog similar to aminocaproic acid that inhibits fibrinolysis and has similar indications?
Valproic acid
Tolfenamic acid
Tranexamic acid
Zoledronic acid
The correct answer is C. Tranexamic acid is a synthetic lysine analog that inhibits conversion of plasminogen to plasmin, therefore inhibiting fibrinolysis. Tranexamic acid binds to the plasminogen lysine binding site, rendering plasminogen unable to bind fibrin and form plasmin. In dogs, tranexamic acid is 4 times more potent than aminocaproic acid.21 Either aminocaproic or tranexamic acid is an appropriate antifibrinolytic in dogs.
Valproic acid is an anticonvulsant drug uncommonly used in veterinary medicine due to cost and potential hepatotoxicity.22 Tolfenamic acid is an NSAID,23 and zoledronic acid is a parenteral bisphosphonate used in the treatment of hypercalcemia and for adjunctive analgesia for bone pain in dogs with osteosarcoma.24
The correct answer is C. Tranexamic acid is a synthetic lysine analog that inhibits conversion of plasminogen to plasmin, therefore inhibiting fibrinolysis. Tranexamic acid binds to the plasminogen lysine binding site, rendering plasminogen unable to bind fibrin and form plasmin. In dogs, tranexamic acid is 4 times more potent than aminocaproic acid.21 Either aminocaproic or tranexamic acid is an appropriate antifibrinolytic in dogs.
Valproic acid is an anticonvulsant drug uncommonly used in veterinary medicine due to cost and potential hepatotoxicity.22 Tolfenamic acid is an NSAID,23 and zoledronic acid is a parenteral bisphosphonate used in the treatment of hypercalcemia and for adjunctive analgesia for bone pain in dogs with osteosarcoma.24
The correct answer is C. Tranexamic acid is a synthetic lysine analog that inhibits conversion of plasminogen to plasmin, therefore inhibiting fibrinolysis. Tranexamic acid binds to the plasminogen lysine binding site, rendering plasminogen unable to bind fibrin and form plasmin. In dogs, tranexamic acid is 4 times more potent than aminocaproic acid.21 Either aminocaproic or tranexamic acid is an appropriate antifibrinolytic in dogs.
Valproic acid is an anticonvulsant drug uncommonly used in veterinary medicine due to cost and potential hepatotoxicity.22 Tolfenamic acid is an NSAID,23 and zoledronic acid is a parenteral bisphosphonate used in the treatment of hypercalcemia and for adjunctive analgesia for bone pain in dogs with osteosarcoma.24
The correct answer is C. Tranexamic acid is a synthetic lysine analog that inhibits conversion of plasminogen to plasmin, therefore inhibiting fibrinolysis. Tranexamic acid binds to the plasminogen lysine binding site, rendering plasminogen unable to bind fibrin and form plasmin. In dogs, tranexamic acid is 4 times more potent than aminocaproic acid.21 Either aminocaproic or tranexamic acid is an appropriate antifibrinolytic in dogs.
Valproic acid is an anticonvulsant drug uncommonly used in veterinary medicine due to cost and potential hepatotoxicity.22 Tolfenamic acid is an NSAID,23 and zoledronic acid is a parenteral bisphosphonate used in the treatment of hypercalcemia and for adjunctive analgesia for bone pain in dogs with osteosarcoma.24
What is the most common adverse effect of tranexamic acid?
Vomiting
Type I hypersensitivity reaction
Hemorrhage
Pain at the injection site
The correct answer is A. Vomiting is a dose-related adverse effect that is most likely to occur after rapid IV bolus administration of tranexamic acid. Aminocaproic acid, however, results in GI irritation in <1% of dogs that receive this drug. Tranexamic acid induces emesis via NK1-receptor agonism25 and has been suggested as an emetic agent in dogs that recently ingested toxins or foreign objects.26 In a study, a single dose of 50 mg/kg IV induced emesis in all dogs.25 Emetic effects typically occur within ≈2 minutes of administration; emesis is short lived, as most dogs vomit only twice and vomiting ceases within ≈4 minutes of administration.25
Tranexamic acid is contraindicated in patients that are hypersensitive to this drug or the ingredients in its formulation. However, type I hypersensitivity reactions are not commonly observed.26,27
Hemorrhage is not an adverse effect of tranexamic acid. Because tranexamic acid increases clot strength and prevents clot lysis, thrombotic events are a possible consequence of this drug. Tranexamic acid and aminocaproic acid are contraindicated in patients with a history of, predisposition to, or current diagnosis of thromboembolic disease.27
Injection site pain has not been reported with tranexamic acid administration; however, musculoskeletal pain in humans has been associated with this medication.27
The correct answer is A. Vomiting is a dose-related adverse effect that is most likely to occur after rapid IV bolus administration of tranexamic acid. Aminocaproic acid, however, results in GI irritation in <1% of dogs that receive this drug. Tranexamic acid induces emesis via NK1-receptor agonism25 and has been suggested as an emetic agent in dogs that recently ingested toxins or foreign objects.26 In a study, a single dose of 50 mg/kg IV induced emesis in all dogs.25 Emetic effects typically occur within ≈2 minutes of administration; emesis is short lived, as most dogs vomit only twice and vomiting ceases within ≈4 minutes of administration.25
Tranexamic acid is contraindicated in patients that are hypersensitive to this drug or the ingredients in its formulation. However, type I hypersensitivity reactions are not commonly observed.26,27
Hemorrhage is not an adverse effect of tranexamic acid. Because tranexamic acid increases clot strength and prevents clot lysis, thrombotic events are a possible consequence of this drug. Tranexamic acid and aminocaproic acid are contraindicated in patients with a history of, predisposition to, or current diagnosis of thromboembolic disease.27
Injection site pain has not been reported with tranexamic acid administration; however, musculoskeletal pain in humans has been associated with this medication.27
The correct answer is A. Vomiting is a dose-related adverse effect that is most likely to occur after rapid IV bolus administration of tranexamic acid. Aminocaproic acid, however, results in GI irritation in <1% of dogs that receive this drug. Tranexamic acid induces emesis via NK1-receptor agonism25 and has been suggested as an emetic agent in dogs that recently ingested toxins or foreign objects.26 In a study, a single dose of 50 mg/kg IV induced emesis in all dogs.25 Emetic effects typically occur within ≈2 minutes of administration; emesis is short lived, as most dogs vomit only twice and vomiting ceases within ≈4 minutes of administration.25
Tranexamic acid is contraindicated in patients that are hypersensitive to this drug or the ingredients in its formulation. However, type I hypersensitivity reactions are not commonly observed.26,27
Hemorrhage is not an adverse effect of tranexamic acid. Because tranexamic acid increases clot strength and prevents clot lysis, thrombotic events are a possible consequence of this drug. Tranexamic acid and aminocaproic acid are contraindicated in patients with a history of, predisposition to, or current diagnosis of thromboembolic disease.27
Injection site pain has not been reported with tranexamic acid administration; however, musculoskeletal pain in humans has been associated with this medication.27
The correct answer is A. Vomiting is a dose-related adverse effect that is most likely to occur after rapid IV bolus administration of tranexamic acid. Aminocaproic acid, however, results in GI irritation in <1% of dogs that receive this drug. Tranexamic acid induces emesis via NK1-receptor agonism25 and has been suggested as an emetic agent in dogs that recently ingested toxins or foreign objects.26 In a study, a single dose of 50 mg/kg IV induced emesis in all dogs.25 Emetic effects typically occur within ≈2 minutes of administration; emesis is short lived, as most dogs vomit only twice and vomiting ceases within ≈4 minutes of administration.25
Tranexamic acid is contraindicated in patients that are hypersensitive to this drug or the ingredients in its formulation. However, type I hypersensitivity reactions are not commonly observed.26,27
Hemorrhage is not an adverse effect of tranexamic acid. Because tranexamic acid increases clot strength and prevents clot lysis, thrombotic events are a possible consequence of this drug. Tranexamic acid and aminocaproic acid are contraindicated in patients with a history of, predisposition to, or current diagnosis of thromboembolic disease.27
Injection site pain has not been reported with tranexamic acid administration; however, musculoskeletal pain in humans has been associated with this medication.27
Aminocaproic acid has been proven to be effective in the treatment of which veterinary condition?
Hemorrhagic pericardial effusion secondary to a right atrial mass
Indolent corneal ulcers
Exercise-induced pulmonary hemorrhage in horses
Degenerative myelopathy in German shepherd dogs
The correct answer is B. Topical aminocaproic acid is effective in the treatment of persistent corneal epithelial defects (ie, indolent ulcers, superficial chronic corneal epithelial defects). In a study, after removal of nonadherent epithelium, 94% of eyes treated with aminocaproic acid healed as compared with only 41% of eyes that healed when treated with gentamicin ophthalmic solution.28 Persistent corneal epithelial erosion is suspected to occur secondary to high ocular surface plasmin levels that degrade extracellular matrix proteins essential to epithelial migration and corneal healing. Inhibiting plasmin activation allows more rapid re-epithelialization and adhesion of the new epithelium.
In a study of dogs with hemorrhagic pericardial effusion secondary to a right atrial mass, administration of aminocaproic acid, Yunnan Baiyao, or both after pericardiocentesis did not affect the time to recurrence of clinical signs as compared with pericardiocentesis alone.29 Neither drug had a significant effect on survival time. Although both drugs were safe to use, this study concluded that neither aminocaproic acid nor Yunnan Baiyao are effective adjunctive treatments for hemorrhagic pericardial effusion secondary to a right atrial mass.29 Because only a small number of dogs received aminocaproic acid in this study, further investigation is warranted to determine the effectiveness of this drug in treatment of hemorrhagic pericardial effusion.
In a study of horses, aminocaproic acid did not prevent or reduce the severity of exercise-induced pulmonary hemorrhage and failed to improve performance during exercise.30
A study investigating a treatment protocol that consisted of aminocaproic acid; N-acetylcysteine; vitamins B, C, and E; and physiotherapy showed persistent decline in neurologic status of all treated dogs.31 The study concluded that this treatment protocol was not superior to physiotherapy alone.
The correct answer is B. Topical aminocaproic acid is effective in the treatment of persistent corneal epithelial defects (ie, indolent ulcers, superficial chronic corneal epithelial defects). In a study, after removal of nonadherent epithelium, 94% of eyes treated with aminocaproic acid healed as compared with only 41% of eyes that healed when treated with gentamicin ophthalmic solution.28 Persistent corneal epithelial erosion is suspected to occur secondary to high ocular surface plasmin levels that degrade extracellular matrix proteins essential to epithelial migration and corneal healing. Inhibiting plasmin activation allows more rapid re-epithelialization and adhesion of the new epithelium.
In a study of dogs with hemorrhagic pericardial effusion secondary to a right atrial mass, administration of aminocaproic acid, Yunnan Baiyao, or both after pericardiocentesis did not affect the time to recurrence of clinical signs as compared with pericardiocentesis alone.29 Neither drug had a significant effect on survival time. Although both drugs were safe to use, this study concluded that neither aminocaproic acid nor Yunnan Baiyao are effective adjunctive treatments for hemorrhagic pericardial effusion secondary to a right atrial mass.29 Because only a small number of dogs received aminocaproic acid in this study, further investigation is warranted to determine the effectiveness of this drug in treatment of hemorrhagic pericardial effusion.
In a study of horses, aminocaproic acid did not prevent or reduce the severity of exercise-induced pulmonary hemorrhage and failed to improve performance during exercise.30
A study investigating a treatment protocol that consisted of aminocaproic acid; N-acetylcysteine; vitamins B, C, and E; and physiotherapy showed persistent decline in neurologic status of all treated dogs.31 The study concluded that this treatment protocol was not superior to physiotherapy alone.
The correct answer is B. Topical aminocaproic acid is effective in the treatment of persistent corneal epithelial defects (ie, indolent ulcers, superficial chronic corneal epithelial defects). In a study, after removal of nonadherent epithelium, 94% of eyes treated with aminocaproic acid healed as compared with only 41% of eyes that healed when treated with gentamicin ophthalmic solution.28 Persistent corneal epithelial erosion is suspected to occur secondary to high ocular surface plasmin levels that degrade extracellular matrix proteins essential to epithelial migration and corneal healing. Inhibiting plasmin activation allows more rapid re-epithelialization and adhesion of the new epithelium.
In a study of dogs with hemorrhagic pericardial effusion secondary to a right atrial mass, administration of aminocaproic acid, Yunnan Baiyao, or both after pericardiocentesis did not affect the time to recurrence of clinical signs as compared with pericardiocentesis alone.29 Neither drug had a significant effect on survival time. Although both drugs were safe to use, this study concluded that neither aminocaproic acid nor Yunnan Baiyao are effective adjunctive treatments for hemorrhagic pericardial effusion secondary to a right atrial mass.29 Because only a small number of dogs received aminocaproic acid in this study, further investigation is warranted to determine the effectiveness of this drug in treatment of hemorrhagic pericardial effusion.
In a study of horses, aminocaproic acid did not prevent or reduce the severity of exercise-induced pulmonary hemorrhage and failed to improve performance during exercise.30
A study investigating a treatment protocol that consisted of aminocaproic acid; N-acetylcysteine; vitamins B, C, and E; and physiotherapy showed persistent decline in neurologic status of all treated dogs.31 The study concluded that this treatment protocol was not superior to physiotherapy alone.
The correct answer is B. Topical aminocaproic acid is effective in the treatment of persistent corneal epithelial defects (ie, indolent ulcers, superficial chronic corneal epithelial defects). In a study, after removal of nonadherent epithelium, 94% of eyes treated with aminocaproic acid healed as compared with only 41% of eyes that healed when treated with gentamicin ophthalmic solution.28 Persistent corneal epithelial erosion is suspected to occur secondary to high ocular surface plasmin levels that degrade extracellular matrix proteins essential to epithelial migration and corneal healing. Inhibiting plasmin activation allows more rapid re-epithelialization and adhesion of the new epithelium.
In a study of dogs with hemorrhagic pericardial effusion secondary to a right atrial mass, administration of aminocaproic acid, Yunnan Baiyao, or both after pericardiocentesis did not affect the time to recurrence of clinical signs as compared with pericardiocentesis alone.29 Neither drug had a significant effect on survival time. Although both drugs were safe to use, this study concluded that neither aminocaproic acid nor Yunnan Baiyao are effective adjunctive treatments for hemorrhagic pericardial effusion secondary to a right atrial mass.29 Because only a small number of dogs received aminocaproic acid in this study, further investigation is warranted to determine the effectiveness of this drug in treatment of hemorrhagic pericardial effusion.
In a study of horses, aminocaproic acid did not prevent or reduce the severity of exercise-induced pulmonary hemorrhage and failed to improve performance during exercise.30
A study investigating a treatment protocol that consisted of aminocaproic acid; N-acetylcysteine; vitamins B, C, and E; and physiotherapy showed persistent decline in neurologic status of all treated dogs.31 The study concluded that this treatment protocol was not superior to physiotherapy alone.
Quiz: Use of Epsilon Aminocaproic Acid
Final scoreReferences
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