Thrombosis in Veterinary Medicine
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Questions and Answers

What is a characteristic of direct Xa inhibitors like Rivaroxaban and Apixaban?

  • Have predictable pharmacokinetics that are not impacted by food (correct)
  • Require antithrombin for effectiveness
  • Inhibit only free Xa in the bloodstream
  • Provide reversible inhibition of Factor Xa
  • Which anticoagulant has been recommended for cats to prevent ATE?

  • Heparin
  • Aspirin
  • Warfarin
  • Clopidogrel (correct)
  • What is a potential drawback of using direct Factor Xa inhibitors?

  • They are ineffective for preventing ATE
  • They provide irreversible inhibition of Factor Xa (correct)
  • They cause an unpredictable response to food intake
  • They require daily blood monitoring
  • In the context of ATE recurrence in cats, what was the median time with clopidogrel in the FATCAT study?

    <p>443 days (C)</p> Signup and view all the answers

    Which combination therapy case report showed a specific median time to ATE recurrence?

    <p>Dual therapy of Rivaroxaban and Clopidogrel (B)</p> Signup and view all the answers

    What condition is NOT associated with an increased risk of thrombosis in animals?

    <p>Asthma (B)</p> Signup and view all the answers

    What factor worsens the prognosis in cases of sepsis?

    <p>Presence of coagulopathy (C)</p> Signup and view all the answers

    Which condition is a known risk factor for jugular thrombophlebitis in horses?

    <p>Colitis (B)</p> Signup and view all the answers

    Which scenario is a primary indication for anticoagulant drugs?

    <p>Animals with a single strong risk factor (A)</p> Signup and view all the answers

    Which of the following is NOT typically a risk factor for thrombosis related to catheter use?

    <p>Standard needle procedures (C)</p> Signup and view all the answers

    In which animal condition is anticoagulation always indicated?

    <p>Dogs with IMHA (A)</p> Signup and view all the answers

    Which gastrointestinal disease is associated with an increased risk of thrombosis in horses?

    <p>Duodenitis (A)</p> Signup and view all the answers

    What is a common cause of cerebrovascular disease?

    <p>Thrombotic events (A)</p> Signup and view all the answers

    Which of the following is NOT a characteristic sign of thrombosis during a physical exam?

    <p>Increased pulse in the affected area (C)</p> Signup and view all the answers

    What is a major consequence of thrombosis that may lead to sudden death?

    <p>Massive thrombosis (A)</p> Signup and view all the answers

    Which diagnosis method is used to identify thrombi in situ?

    <p>Ultrasound or other imaging methods (A)</p> Signup and view all the answers

    What causes pulmonary thromboembolism?

    <p>Acute onset dyspnea (A)</p> Signup and view all the answers

    Which of the following factors is NOT part of Virchow's theory of hypercoagulability?

    <p>Increased heart rate (A)</p> Signup and view all the answers

    Which condition is indicated by thrombophlebitis?

    <p>Warmth and swelling over the vein (C)</p> Signup and view all the answers

    What is a consequence of endothelial dysfunction related to thrombosis?

    <p>Exposure of procoagulant triggers (A)</p> Signup and view all the answers

    Which organ dysfunction is primarily linked with microthrombosis?

    <p>Acute kidney injury (A)</p> Signup and view all the answers

    What condition can lead to an increased risk of thrombosis due to elevated procoagulant proteins?

    <p>Sepsis (A)</p> Signup and view all the answers

    Which of the following is a characteristic of arterial clots?

    <p>Predominantly platelets (A)</p> Signup and view all the answers

    What contributes to the hypercoagulable state by decreasing anticoagulant proteins?

    <p>Loss related to conditions like GI diseases (D)</p> Signup and view all the answers

    What is the effect of blood stasis on the coagulation pathway?

    <p>Activation of intrinsic pathway (B)</p> Signup and view all the answers

    Which type of clots are typically formed in low-pressure environments and are rich in fibrin?

    <p>Red clots (C)</p> Signup and view all the answers

    In feline cardiac disease, which factor is a significant risk for thrombosis?

    <p>Left atrial dilation (A)</p> Signup and view all the answers

    Which of the following factors is likely to activate intrinsic pathway thrombosis?

    <p>Decreased blood flow (C)</p> Signup and view all the answers

    Antiplatelet agents are primarily used for which type of clots?

    <p>Arterial clots (A)</p> Signup and view all the answers

    Which condition has a strong risk of thrombosis that warrants anticoagulant consideration?

    <p>IMHA (D)</p> Signup and view all the answers

    Which condition has an insufficient risk of thrombosis according to the data provided?

    <p>PSS (Portosystemic Shunt) (A)</p> Signup and view all the answers

    For which condition is it recommended to use antithrombotic agents despite having a weak risk factor for thrombosis?

    <p>IMHA (cats) (C)</p> Signup and view all the answers

    What is a common feature of both pancreatitis and hyperadrenocorticism in relation to thrombosis risk?

    <p>Both are categorized under insufficient evidence for thrombosis risk. (A)</p> Signup and view all the answers

    Which condition poses a moderate to strong risk of thrombosis according to available evidence?

    <p>Heartworm (C)</p> Signup and view all the answers

    What is stated about the superiority of anticoagulant drugs in veterinary medicine?

    <p>No clear evidence shows one drug or class superior to another. (D)</p> Signup and view all the answers

    Which condition is associated with an individual variable risk of thrombosis?

    <p>Sepsis (D)</p> Signup and view all the answers

    Which of the following correctly identifies a condition where antithrombotics are not recommended?

    <p>PSS (dog) (D)</p> Signup and view all the answers

    What is a potential complication of using unfractionated heparin (UFH) in horses?

    <p>Erythrocyte agglutination and thrombocytopenia. (B)</p> Signup and view all the answers

    Which of the following is NOT a characteristic of Low Molecular Weight Heparin (LMWH)?

    <p>Can be administered intravenously or subcutaneously. (B)</p> Signup and view all the answers

    How does heparin affect hyperlipidemia?

    <p>Increases the release of lipoprotein lipase and hepatic lipase. (C)</p> Signup and view all the answers

    Which of the following is a potential use of LMWH in horses?

    <p>Prevention of platelet activation from EHV-1. (A)</p> Signup and view all the answers

    What is a significant advantage of LMWH over UFH in treating thrombosis?

    <p>LMWH has a longer half-life, requiring less frequent dosing. (D)</p> Signup and view all the answers

    What is the primary mechanism by which heparin exerts its antithrombotic effect?

    <p>Potentiating the activity of antithrombin. (B)</p> Signup and view all the answers

    What does the phrase "individual variation in optimal UFH dose likely" mean?

    <p>Different horses require different doses of UFH for the same therapeutic effect. (A)</p> Signup and view all the answers

    How can the effectiveness of LMWH be measured?

    <p>By measuring the activity of Factor Xa in the blood. (D)</p> Signup and view all the answers

    Flashcards

    Thrombosis Risk in IMHA

    IMHA (Immune-Mediated Hemolytic Anemia) has a strong risk of thrombosis.

    Thrombosis Risk in PLN (Dogs)

    Dogs with PLN (Protein-Losing Nephropathy) have a yes risk for thrombus formation.

    Thrombosis Risk in Pancreatitis

    Pancreatitis presents a yes risk for thrombosis in affected animals.

    Thrombosis in Neoplasia

    Neoplasia (cancer) poses a yes risk for thrombosis.

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    Thrombosis Risk in Feline Heart Disease

    Feline heart disease is strongly associated with thrombosis risk.

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    Antithrombotics Recommendation for Heartworm

    Heartworm has a 'yes' recommendation for antithrombotics due to thrombosis risk.

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    Anticipating Thrombosis in IMHA (Cats)

    Cats with IMHA have a weak risk for thrombosis but still considered for treatment.

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    Antithrombotic Classes

    Antithrombotic drugs include antiplatelet, anticoagulant, and fibrinolytic agents.

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    Direct Xa inhibitors

    Medications like Rivaroxaban and Apixaban that inhibit Factor Xa directly, without needing antithrombin.

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    Predictable pharmacokinetics

    Direct Xa inhibitors have consistent absorption and their effectiveness isn't affected by food intake.

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    Irreversible inhibition

    Direct Xa inhibitors permanently inhibit Factor Xa, complicating rapid drug effect reversal.

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    Clopidogrel in cats

    Clopidogrel is recommended for the prevention of ATE in cats, showing longer recurrence times compared to Aspirin.

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    Combination therapy in cats

    Case reports suggest dual therapy with Rivaroxaban and Clopidogrel could extend the time to ATE recurrence in cats.

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    Hypercoagulable state

    A condition with increased procoagulant proteins, leading to a higher risk of blood clots.

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    Procoagulant proteins

    Proteins that promote blood clotting; increase in certain conditions like sepsis or surgery.

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    Anticoagulant proteins

    Proteins that prevent blood coagulation; their decrease raises clotting risk.

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    Blood stasis

    A condition of decreased or abnormal blood flow, promoting clot formation.

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    Intrinsic pathway

    The clotting process activated in response to blood vessel injury, decreasing blood flow.

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    Arterial clots

    Clots formed in arteries, primarily made up of platelets and activated by high shear flow.

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    Venous clots

    Clots formed in veins, rich in fibrin and erythrocytes, occurring due to low pressure.

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    Feline cardiac disease

    Heart issues in cats, marked by dilation of the left atrium, affecting blood flow.

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    Septic peritonitis risk

    Septic dogs without coagulopathy are at risk of thrombosis.

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    Neonatal sepsis

    A condition in foals that can worsen prognosis if coagulopathy is present.

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    Jugular thrombophlebitis

    Inflammation of the jugular vein, often in horses post-colic treatment.

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    Cancer and thrombosis

    Carcinomas in dogs are associated with an increased risk of thrombosis.

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    Indications for anticoagulants

    Required in animals with existing thrombi or multiple moderate risk factors.

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    Cerebrovascular disease

    Can result from a thrombotic event rather than causing it.

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    Extracorporeal circuits risk

    Dialysis activates coagulation during treatment, increasing thrombus risk.

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    Antithrombotics guideline

    CURATIVE guidelines recommend antithrombotics for certain high-risk cases.

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    Heparin

    An anticoagulant that potentiates antithrombin inhibition.

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    Unfractionated Heparin (UFH)

    Heparin type that binds to antithrombin and factors IIa, Xa.

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    Low-Molecular Weight Heparin (LMWH)

    Heparin form that primarily binds to factor Xa.

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    Dalteparin

    A type of LMWH used for anticoagulation.

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    Enoxaparin

    Another LMWH, similar uses as dalteparin.

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    Anti-Xa activity

    Measurement used to dose heparin effectively.

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    Erythrocyte agglutination

    Clumping of red blood cells, a side effect of UFH in horses.

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    Hyperlipemia treatment

    Heparin helps release lipoprotein and hepatic lipase in horses.

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    Thrombosis

    Formation of a blood clot inside a blood vessel, obstructing flow.

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    Thromboembolism

    A condition where a clot breaks free and travels to block another vessel.

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    Obstructive shock

    Shock due to impaired blood flow affecting oxygen delivery to organs.

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    Microthrombosis

    Small blood clots formed in the microcirculation, often causing organ dysfunction.

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    Ischemic myopathy

    Painful and hard muscles due to reduced blood flow from thrombosis.

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    Thrombophlebitis

    Inflammation of a vein with a clot, presenting warmth and swelling.

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    Pulmonary thromboembolism

    Blockage of a pulmonary artery by a clot, leading to sudden breathing difficulties.

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    Hypercoagulability

    A state where blood is more prone to clotting than normal, increasing thrombosis risk.

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    Study Notes

    Thrombosis in Veterinary Medicine

    • Thrombosis and thromboembolism
      • Obstructive shock
      • Impaired regional oxygen delivery
      • Impaired blood flow
      • Organ dysfunction/failure
      • Primarily microthrombosis
      • Complications of therapy, e.g., catheter associated thrombosis

    Diagnosis of Thrombosis

    • Physical exam
      • Affected extremity is often colder than others
      • Ischemic muscles are painful and hard (ischemic myopathy)
      • Thrombophlebitis (warmth and swelling over a vein, usually at site of prior venipuncture or catheter)
    • Signs of organ failure
    • Pulmonary thromboembolism (characterized by acute dyspnea)
    • Acute kidney injury
    • Hepatic injury
    • Stroke or other acute neurologic decline
    • Sudden death may occur from massive thrombosis
    • Ultrasound or other imaging (e.g. CT) may identify thrombi in situ

    Hypercoagulability: Theory

    • Virchow (circa 1845)
      • Endothelial damage
      • Hypercoagulable state
      • Blood stasis/ alterations in blood flow

    Endothelial Dysfunction

    • Alterations of glycocalyx exposing procoagulant triggers
    • Inflammation
    • Fluid therapy
    • Direct injury
    • Release of von Willebrand factor (vWF)
    • Activated endothelial cell

    Hypercoagulable State

    • Increased procoagulant proteins
      • Sepsis
      • Inflammation
      • Surgery, including surgery for fibrinogen
      • Hyperadrenocorticism (heredity may be a factor)
      • Increased heritability
    • Decreased anticoagulant proteins
      • Sepsis
      • Inflammation
      • Gastrointestinal (GI) disease
      • Renal disease

    Blood Stasis

    • Activation of intrinsic pathway
    • Decreased blood flow
    • Abnormal blood flow
    • Intravascular foreign material
    • Negative charge
    • Biofilm production

    Arterial vs Venous Thrombosis

    • Arterial clots ("white clots")
      • Predominantly platelets
      • Activated with high shear blood flow
      • Antiplatelet agents are the primary therapy
    • Venous clots ("red clots")
      • Low pressure/venous stasis
      • Rich in fibrin, erythrocytes
      • Anticoagulant agents are the primary therapy

    Cardiac Disease

    • Feline cardiac disease
      • Left atrial dilation
      • Spontaneous echocontrast
      • Reduced left atrial appendage flow velocity
      • Thromboembolic sequelae (primarily arterial thromboembolism (ATE)).
    • Heartworm (pulmonary artery thrombosis)
    • Worm thrombus vs. clot
    • Transvenous pacemakers
    • Uncommon clot formation on leads

    Immune-mediated Hemolytic Anemia (IMHA)

    • Strongly associated with thrombosis in dogs
    • Anticoagulation is standard therapy component
    • Risk factors include:
      • Severe inflammatory response
      • High fibrinogen, decreased antithrombin
      • RBC membranes in the circulation
      • Corticosteroid therapy
      • IV access, sometimes multiple
      • Multiple blood transfusions

    Protein Losing Conditions

    • Protein losing nephropathy (PLN)
      • Associated with thrombosis
      • Possibly due to loss of antithrombin
    • Protein losing enteropathy (PLE)
      • Loss of proteins including antithrombin
      • Small and large animals

    Glucocorticoids, Hyperadrenocorticism

    • Treatment with corticosteroids is associated with a hypercoagulable state
    • Risk of thrombosis with hyperadrenocorticism (dogs)

    Infectious Disease

    • Dogs with sepsis (especially endocarditis, septic peritonitis, aspiration pneumonia) without coagulopathy are at risk of thrombosis
    • Does not support routine anticoagulation in septic dogs
    • Neonatal sepsis (foals)
    • Presence of coagulopathy worsens prognosis
    • EHV-1 infection (adult horses)
    • Vasculitis, thrombosis → myeloencephalopathy

    Equine Gastrointestinal Disease

    • Jugular thrombophlebitis or other thrombosis
    • Ischemic/strangulating Gl lesions
    • Colitis
    • Duodenitis/proximal jejunitis
    • Right dorsal colitis
    • Jugular thrombophlebitis is more likely in horses with surgically treated colic that develop fever or diarrhea.
    • Salmonellosis (also a risk factor)
    • Thrombosis may initiate at venipuncture site or on catheter

    Other Conditions

    • Neoplasia
      • Carcinomas in dogs are associated with a risk of thrombosis.
      • Overall prevalence is unknown.
    • Cerebrovascular disease
      • May result from a thrombotic event (rather than cause).
    • Pancreatitis (dogs)
    • Extracorporeal circuits (e.g., dialysis)
      • Activates coagulation during treatment

    Vascular Access/Devices

    • Transvenous pacemaker leads
    • IV catheters
    • Central lines
    • Catheter-associated thrombi are common in patients with severe inflammation.
    • Consideration of the number and type of venous catheter is important
    • Catheter alone is not usually a risk factor.

    When are Anticoagulant Drugs Indicated?

    • Animals with existing thrombi/thromboembolism
    • Animals with a single strong risk factor
    • Animals with multiple moderate risk factors
    • Always indicated for dogs with IMHA, cats with heart disease

    Disease Risk Factor Summary

    • Table summarizes conditions, thrombosis risk levels, and recommended anticoagulation use.

    Anticoagulant Drugs

    • Absence of clear evidence for any single drug/class superiority
    • Specific mechanisms (e.g., platelet vs factor)
    • Ease of administration; cost

    Acetylsalicylic Acid (ASA; Aspirin)

    • Inhibits cyclooxygenase (COX)
      • Prevents production of AA metabolite thromboxane (TXA2)
      • Thromboxane is a potent platelet agonist, vasoconstrictor
      • Irreversible COX inhibition
    • Decreases platelet aggregation in dogs
    • Does reliably impact platelet aggregation in cats or horses

    FAT-CAT: Aspirin vs Clopidogrel

    • Prevention of recurrent ATE in cats
    • 42 dogs, 18.75 mg po q24
    • 43 ASA, 81mg po q72h
    • Recurrent TE in:
    • 19/39 clopidogrel (49%)
    • 27/36 ASA (75%)
    • Median time to recurrence
    • 443 days, (7-990 days) clopidogrel
    • 192 days, (6-883 days) ASA

    Heparin

    • Potentiates AT inhibition (unfractionated heparin (UFH))
    • Binds antithrombin (AT) and Flla, FXa
    • Low-Molecular weight heparin (LMWH)
      • Binds Xa
        • Dalteparin
        • Enoxaparin
    • Can measure anti-Xa activity to dose either directly
    • Directly correlated to drug

    Types of Heparins

    • Unfractionated Heparin (UFH)
      • In dogs/cats/horses with risk of thrombosis
      • Variability in optimal UFH dose
      • Interactions with plasma proteins, endothelial cells, macrophages
      • Bleeding - less specific binding to clotting factors (esp. lla)
      • Erythrocyte agglutination and thrombocytopenia (horses)
    • Low molecular weight heparin (LMWH)
      • Used in dogs, cats, and horses with variable dosing regimens
      • More frequent dosing is often needed to achieve similar efficacy compared to humans
      • More predictable PK/PD
      • Not associated with RBC agglutination in horses

    Other Uses for Heparin in Horses

    • Hyperlipemia
      • Increased release of lipoprotein lipase
      • Increased release of hepatic lipase
      • LMWH may prevent platelet activation from EHV-1
      • Adhesion prevention: effective

    Direct Xa Inhibitors

    • Rivaroxaban (Xarelto); apixaban (Elliquis)
      • Inhibit Factor Xa directly
      • No need for antithrombin
      • Predictable pharmacokinetics
      • Irreversible inhibition of Factor Xa
      • Well-tolerated in dogs and cats

    Antiplatelet Agents vs Anticoagulants for ATE

    • Dogs
      • Antiplatelet agents may be more effective
      • Anticoagulants also effective
    • Cats
      • Clopidogrel recommended for ATE prevention.

    Combination Therapy

    • Combination associated with high incidence of bleeding complications
    • Especially GI (PPI is recommended)
    • Clopidogrel preferred over ASA
    • Deescalate therapy (often antiplatelet drug) after acute need, based on risk
    • Coadministration of rivaroxaban/clopidogrel (rare)
    • Bleeding in one dog (0.8mg/kg RVX, 4mg/kg clopid)
    • 0.5 mg/kg RVX, 2mg/kg clopidogrel is successful treatment
    • Coadministration of apixaban/clopidogrel
      • Apixaban up to 1 mg/kg PO q12h; clopidogrel 1.875 mg/kg PO q24h
    • Appears safe in healthy dogs

    Fibrinolytic Drugs

    • Tissue plasminogen activator (tPA)
      • Injectable activator of plasmin
      • Rapid effect: may cause reperfusion injury
      • Breaks down all clots
      • Catheter-delivered
      • May be superior

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    Description

    Explore the critical concepts of thrombosis and thromboembolism in veterinary medicine. This quiz covers diagnosis, symptoms, and the implications of thrombosis in animals. Test your knowledge on conditions such as obstructive shock and associated organ dysfunction.

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