Abnormal Hemostasis Flashcards
Abnorma Hemostasis
Inadequate hemostasis can lead to hemorrhage
Excessive or inappropriate hemostasis can lead to thrombosis
Platelet Diorders:
- Platelet deficiency:
- decreased production
- excessive utilization
- premature destruction
- Abnormal platelet function (Thrombocytopathy)
Decreased Platelet Numbers
- Adequate numbers of platelets are necessary for successful response to vascular injury
Causes of Thrombocytopenia:
Decreased Production
- Myelophthesis
- Bone marrow neoplasia myelofibrosis
- Chemicals:
- Estrogen, bracken fern, trichothecene mycotoxins
- Drugs:
- Chloramphenicol, sulfonamides, phenybutazone
- Radiation and chemotherapy
Causes of Thrombocytopenia:
Increased consumption
- Endothelial activation:
- Vasculitis, infectious agents.
- localized intravascular coagulation
- vascular neoplasia, hemorrhage, thrombosis
- Disseminated Intravascular Coagulation:
- Endotoxemia, shock
Causes of Throbmycytopenia:
Increased Destruction
- Immune mediated:
- primary
- Secondary:
- Infectious agent or chmical
- Infection:
- BVD virus, Canine distemper virus, canine parvovirus, ehrlichia sp. FIV, FeLV, EIA,
- Thrombocytopenia is often associated with endotoxemia
Abnormal Platelet Function
- Most platelet function defects are associated with an inability to adhere or aggregate at a site of injury
- Other functional defects can affect granule content of the degranulation process
Causes of Thrombocytophathy:
Inherited problems of adhesions
- GpIb deficiency:
- bernard-soulier syndrome of humans
- Defective GPIIb and GPIIa
- glanzmann’s thrombasthenia of humans
- Has been rarely reported in otterhounds and great pyrenees
- Von Willebrand factor deficiency
Von Willebrand Disease
- Most common inherited bleeding disorder of dogs
- Abnormal primary hemostasis due to a functional deficiency of VWF
- platelets do not efficiently bind to damaged endothelium
- Signs include mucosal hemorrhage, bruising and prolonged bleeding
Causes of Thrombocytopathy:
Acquired platelet function problems
- Drugs
- Uremia assocaited with renal failure
- Increased FDPs
- Hepatic disease
- Immune-mediated thrombocytopenia
- Megakaryocytic neoplasia
- Infection
- BVDV and FeLV
Acquired Platelet Dysfunction
Antiplatelet drugs:
Aspirin
Irreversible inhibition of the cyclooxygenase pathway of arachidonic acid metabolism in platelets
Thromboxane A2 synthesis is inhibited
Coagulation Disorders
- Inherited deficiency of coagulation factors
- Acquired coagulation defects
- decreased production due to liver disease
- Vitamin K antagonism or deficiency
- rodenticided, sweet clover poisoning, biliary or bowel disease
- Increased use
- Inhibition of coagulation factors
- heparin, FDPs, antiphospholipid antibody to coagulation factors
Causes of Coagulation Disorders
- Inherited Coagulation Factor deficiencies in animals include:
- Extrinsic pathway:
- Factor VII
- Intrinsic Pathway:
- Prekallikrein and Factors XII, XI, IX, VIII
- Common Pathway:
- Factors X, II, I
- Extrinsic pathway:
Inherited Coagulation Factor Deficiences:
Hemophilia A
- Factor VII deficiency, X-linked recessive
- Most common inherited coagulopathy in animals
- reported in dogs, cats, horses, cattle
- Best documented in dogs (German Shepherd)
- Considerable vairability in the degree of loss of Factor VII activity:
- Mild:
- no spontaneous bleeding and usually maintian normal hemostasis
- Moderate:
- Can have serious hemorrhage after trauma, acheiving hemostasis is prolonged
- Severe:
- Spontaneous bleeding may occur
- Mild:
Inherited Coagulation Factor Deficiencies:
Intrinsic:
Hemophilia B
- Factor IX deficiency, x-linked recessive
- Reported in dogs and cats
- Similar signs to Hemophilia A
- Most cases Factor IX activity is very low
Inherited Coagulation Factor Deficiencies:
Intrinsic:
Hemophilia A and B
- In these conditions the female is an unaffected carrier
- The male may or may not be affected
- When a female carrier is mated to an unaffected male, 50% will get a defective X chromosome.
Acquired Coagulation Disorders
- Decreased production
- extensive liver disease
- Vitamin K deficiency
- Increased Utilization
- widespread endothelial injury
- severe trauma or burns
- Disseminated intravascular Coagulation
- Inhibition of coagulation factors
- heparin, FDPs, Antiphospholipid antibody, antibody to coagulation factors
Acquired Coagulation Disorders:
Liver Disease
- Decreased production of both pro- and anti- coagulation factors
- Bleeding is uncommon unless liver disease is severe or associated with DIC
Acquired Coagulation Disorders:
Vitamin K deficiency
- Antagonists inhibit conversion of oxidized vitamin K to reduced (Active) form
- These include:
- moldy sweet clover
- Rodenticides
- Sulfaquinoxaline and other drugs
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Acquired Coagulation Disorder:
Increased Utilization
Widespread endothelial injury
Severe Trauma or burns
Disseminated Intravascular Coagulation
Hemostatic Dyshomeostasis:
Disseminated Intravascular Coagulation
- DIC is a profound disruption of hemostasis
- Major stimulus is widespread vascular injury
- can occur as a priamry event
- Commonly occurs as a termianl event in shock
Disseminated Intravascular Coagulation
- Fundamental change is accelerated or unbalanced coagulation
- there are elevated levels of both procoagulation and fibrinolytic substances
- Thrombin plays a central role in DIC
- activated platelets and coagulation factors
- activates fibrinolysis
DIC:
Morphology
There are subclinical to severe hemorrhage
Shock
Organ failure
DIC:
significance
Is a life-threatening and rapidly progressing event
one of the most dramatic examples of dyshomeostasis in animals
Abnormal Hemostasis:
Hemorrhage
the loss of blood from the vessel into extravascular sites
Hemorrhage:
Causes
Vascular Injury
Platelet Disorders
Coagulation Disorders
Causes of Vascular Injury
- Trauma
- Inflammation
- infectious
- non-infectious
- Secondary invasion
- inflammatory or neoplasitc
- Necrosis
- toxins
- Infectious agents
- Endothelial degeneration
- endotoxin (LPS)
Causes of Platelet Disorders
- Platelet deficiency:
- decreased production
- bone marrow injury
- Excessive utilization
- widespread injury or DIC
- Premature destruction
- damage due to viruses, or other infectious agents
- Immune-mediated
- Abnormal platelet function (Thrombocytopathy)
- decreased production
Causes of Coagulation Disorders
- Inherited deficiency of coagulation factors
- Acquired coagulation defects
- decreased production due to liver disease
- Vitamin K antagonism
- Increased use
- Inhibition of coagulation factors
Hemorrhage:
Pathogensis
- By rhexis:
- Active blood loss due to tears or rents in the blood vessel
- By Diapedesis:
- Passive blood loss through endothelial gaps
Hemorrhage:
Morphology
- Red irregular foci in tissues characterized by extravascular erythrocytes
- Classification:
- petechia
- Ecchymosis
- Suffusive
Hemorrhage:
Morphology:
Petechia
pinpoint (1-2mm) hemorrhage usually assocaited with mild injury and diapedesis
Hemorrhage:
Morphology:
Eccymosis
Medium (2-3cm) hemorrhage assocaited with more severe vascular injury
Hemorrhage:
Morphology:
Suffusive (Paint Brush)
Large localized hemorrhage
Hemorrhage:
Morphology:
Into a body cavity
Hemopericardium
Hemothorax
Hemoperitoneum
Hematoma
Hemorrhage inot tissue or interstitium
An extravascular coagulum of blood
Hemorrhage:
Significance
- Can be insignificant to life-threatening
- Factors influencing clinical outcome:
- Location
- Vital vs. non-vital tissues and organs
- Volume:
- Loss of large blood volumes can lead to shock
- Rate of loss
- Slow rates of loss can have some compensation
- Location
Abnormal Hemostasis:
Thrombosis
- The formation of a solid mass of blood components within a blood vessel or the heart
- Thrombosis is a reflection of excessive or inappropriate hemostasis
Thrombosis:
Causes
- Shift in the normal hemostatic balance towards thrombosis
- endothelial activation/injury
- Platelet activation
- Coagulation pathways activated
- Stasis
- Decreased fibrinolysis
- Abnormal Anti-coagulant proteins
- “Virchows Triad”
- Alterations in blood vessels
- Alterations in blood flow
- Alterations in blood coagulability
Thrombosis:
Alterations in blood vessels
- Endothelial injury
- trauma
- Chemical injury
- Drugs
- Inflammation
- Immune reactions
- Toxins
- Normal endothelium is anti-thrombotic
- platelets do not adhere
Thrombosis:
Alterations in Blood Vessels:
Endothelial Injury Causes
- Viruses
- Bacteria
- Fungi
- Nematode parasites
- Immune-mediated vasculitis
- Endotoxin
- Vitamin E/selemium
- DIC
Thrombosis:
Alterations in Blood Flow:
Decreased blood flow / stasis
- Blood viscosity increases
- Endothelium/blood component interactions increase
- Decreased clearance of activated factors
- Decreased local tissue oxygenation
Thrombosis:
Alterations in blood flow:
Turbulent Blood Flow
enhances endothelial/blood component interactions
Thrombosis:
Alterations in blood coagulability
- Hypercoagulation reflects an increase or decrease in concentrations of activated hemostatic proteins
- coagulation factors or coagulation inhibitors
- Most commonly occurs due to increased activation or decrease degradation of pro-coagulant factors
- Enhanced platelet activity can also contribute
Thrombosis:
Alterations in blood coagulability:
Hypercoagulability causes
- Antithrombin deficiency
- Hepatic disease
- Pregnancy
- Nephrotic syndrome/uremia
- Anti-phospholipid antibodies
- Endocrine disease
- diabetes mellitus, hyperadrenocorticism, hypothyroidism
- Neoplasia
Thrombosis:
Alterations in blood coagulability:
Antithrombin deficiency
Causes of deficiency include decreased production due to liver disease, increased loss due to renal disease or enteropathy
Results in a pro-thrombotic state
Thrombosis:
Arterial Thrombi
These form in arteries in association with rapidly flowing blood
Thronbosis:
Venous Thrombi
These form in veins in associates with slow moving blood
Thrombosis:
Cardiac Thormbi
These form in the heart chambers or on the heart valves
Arterial Thrombi:
Morphology
- Generally pale and firm
- Consist of alternating layer of fibrin and platelets
- The often have a head (attached to endothelium) and a tail that grows downstream
Venous Thrombi:
Morphology
- These are dark red and gelatinous
- They consist of fibrin and platelets intermixed with erythrocytes
- Often occlusive form the point of origin
- They look similar to a postmortem clot
Cardiac Thrombi:
Morphology
- Mural cardiac thrombi form in the heart chambers
- these often mold to the outline of the chamber
- Valvular Cardiac thrombi form on the heart valves
- these are pale and irregular, and are often associated with infection of the valve
Thrombus:
Outcomes
Lysis
Propogation and obstruction
Embolism
Organization
Thrombus:
Lysis
- thrombus is removed by the dissolution of the fibrin matrix and the platelet plug
- plasmin is a major participant in the process
- Most common and efficient with new or small thrombi
- Large more mature thrombi are not easily lysed
Thrombus:
Progagation and Obstruction
- Thrombus grows until it obstructs the vessel lumen
- This is most common with venous thrombi
- rapid blood flow past arterial thrombi makes total obstruction more difficult, particularly in larger vessels
- Dependent tissue is often deprived of oxygen
Thrombus:
Embolism
- Occurs when a thrombus or protion of a thrombus breaks loose into the circulation and lodges in another blood vessel
- This can occur with arterial, venous, and cardiac thrombi
- Embolus can damage and occlude the vessel that it lodges within
Thrombus:
Organization
- This is the process of resolution and healing for large thrombi that can not be lysed
- Organization reduces the size of the thrombus and converts it to a fibrous scar
Thrombus:
Organization:
Process
- Endothelium grows over the surface of the thrombus
- Capillaries grow itno the thrombus at it’s point of attachment
- Macrophages and fibroblasts enter the site to remove debris and produce collagen
- New blood vessels can grow into and through the organizing mass (recanalization)
Thrombus:
Significance
- Most significant result of thrombosis is ischemia and infarction
- Clinical significance of thrombi depend on their size, location, and type
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Significance:
Infarction
Pulmonary infarction
Renal infarction
