Abnormal Hemostasis Flashcards
Abnormal Hemostasis
- Hemostasis is a complex balance that once distrubed, can lead to various problems
- Inadequate hemostasis can lead to hemorrhage
- Excessive or inappropriate hemostasis can lead to thrombosis
Platelet disorders
- Platelet deficiency (Thrombocytopenia)
- Decreased production
- Bone marrow injury or susppression
- Excessive utilization
- Widespread injury or Disseminated Intravascular Coagulation (DIC)
- Premature destruction
- Damage due to viruses or other infectious agents
- Immune-mediated
- Decreased production
- Abnormal platelet function (Thromboctopathy)
Decreased Platelet numbers
- Adequate numbers of plateletsare necessary for successful response to vascular injury
- For mild, localized injury, and animals may be slightly thrombocytopenic and still respond adequtely
- For sever, widespread injury, even nd animal that originally had adequate platelet numbers may rapidly deplete the number necesary for succesful response
Cause of Thrombocytopenia
- Decreased production:
- Myelphthesis
- Bone marrow neoplasia, myelofibbrosis
- Chemicals
- Estrogen, bracken fern, trichothecene mycotoxins
- Drugs
- chloramphenicol, sulfonamides, phenylbutazone
- Radiation and chemical durgs
- Myelphthesis
- Increased destruction:
- Immune medaiated - Primary
- sefonday- Infectious aget or chemical drug-inuduced (various antibodies and anti0infalmmaorties
- Infection -
- BVD, virus, canine distemper birus, canin parvovirus, Ehrlichia spl FIV, FELV, EIA, ansaplasma sp. histoplasma capsulateum, Babesia sp..
- Thrombocytopenia is often associated with endotoxemia
- Immune medaiated - Primary
Causes of thrombocytopenia
- Increased Consumption
- Endothelial activation
- Vasculitis: infectiou agents (RMSF, canine herpes, canine adenovirs, Dirofilaria)
- Endocarditis
- Localized intravascular coagulation
- Vascular neoplasia, hemorrhage, thrombosis
- Disseminated Intravascular Coagulation
- Endotoxemia, Shock
- Endothelial activation
Abnormal Platelet function
- Most platelet function defects are associated with an inability to adhere or aggregate at a sigte of injury
- Other functional efects can afffect granule content or the degrnulation process
Causes of Thrombocytopathy
- Inherited problems of adhesion and/or
- Aggregation include;
- GpIbdeficiency
- Bernard-Soulier syndrome of humans
- rarely reported in Otterhounds d Gread Pyreneese dogs and horses
- CA+2 binding domain of GPIIb is defective
- Von WIllebrand Factor deficiency
- GpIbdeficiency
- Acquired platelet function problems include:
- Drugs: anti-inflammatories, anesthetics and antibiotics
- Uremia associated with renal failure
- Increased FDPs
- Hepatic disease
- Immune-mediated thrombocytopeni
- Megakaryocytic neoplasia
- Infection
- BVDV and FeLV
Von Willebrand Disease
- Most common inherited bleeding disorder of dogs
- Gorgi, Doberman Pinsher, GSD, German Shrothaired and Wirehaired pointers, Golden retriever, Shetland sheepdog, and stradard pooddel are commonl affected
- Abnormal primary hemostatis du to functional deficiency of vWF
- Pltelets do not efficiently bind to damage endothelium
- Signs include mucosal hemmorhge, bruising and prolonged bleeding
Aquired Platelet Dysfunction
- Antiplatlet drugs
- Aspirin
- Irreversible inhibition of the cyclooxygenase pathway of arachidonic acid metabolism in platelets
- Thromboxane A2 synthesis is inhibited
- Aspirin
Coagulation Disorders
- Inherited deficiency of coagulation factors
- Acquired coagulation defects
- Decreased production due to liver diease
- Vitamin K antagonism or deficiency
- Rodentifcides, sweet clover poisoning, biliary or bowel diease
- Increased Use (Consumption: DIC)
- Inhibition of coagulation factors
- Heparin, FDPs, antiphospholipid antibody, antibody to coagulation factors
Causes of Coagulation Disorders
- Inhrited Coagulation Factor Deficiencies in andimals include:
- Extrinsic pathway (Factor VII)
- Intrinsic Pathway
- Prekallikrein
- Factors XII, XI, IX, VIII
- Commno Pathway
- Factors X, II, I
Hemophilia A
- Inherited Coagulation Factor Deficiency
- Factor VIII deficieny, X-linked recessive
- Most common inherited coagulopathy in animals
- Reported in dogs, cats, horses, cattle
- Best documented in dogs
- Considerable variability in the degree of loss of Factor VIII activity
- Mild (>5% activity): no spontaneous bleeding and usually maintain normal hemostasis
- Moderate (2-5% activity): Can have serious hemorrhage after trauma, achieving hemostasis is prolonged
- Severe (<2% activity): Spontaneous bleeding may occur
Hemophilia B
“Christmas Disease”
- Intrinsic Inherited Coagulation Factor Deficiency
- Factor IX deficiency, X-linked recessive
- Reported in DOgs and cats
- Similar signs to Hemophilia A
- In most cases, Factor IX activity is very low
- It lacks the variability in activity associated with Factr VIII in hemophilia A
X-linked Inherited Coagulation Factor Deficiencies
- In these conditions the female is an unaffected carrier
- Males may or may not be affected
- When a female carrier is crossed with an unaffected male:
- 50% of offspring will get defective X
- 50% of females will be carriers
- 50% of males will be affected
- 50% of offspring will get defective X
Severity of Inherited Coagulation Factor Deficiencies
- Many deficiencies are autosomal recessive (incomplete penetrance)
- Severity varies based on inheritance pattern:
- Homozygous animals typically have 5-10% enzyme activiy
- Heterozygous animals typically have 40-50% enzyme activity
Aquired Coagulation Disorders
- Decreased Production
- Extensive liver disease
- Vitamin K deficiency
- Increased utilization
- Widespread endothelial injury
- Severe trauma or burns
- Disseminated Intravasculatr Coagulation
- Inhibition of coagulation factors
- Heparin, FDPs, antiphospholipid antibody, antibody to coagulation factors
How do Acquired Coagulation DIsorders affect the Liver
- Decreased production fo both pro- and anti- coagulant factors
- Bleeding is uncommon unless liver disease is sever or associated with DIC
Vitamin K antagonist - Acquired Coagulation Disorders
- VitK antagonists inhibit conversion of oxidized vitamin K to reduced (active) form
- reduced vit K is required to interact with Vit K-dependent carboxylase
- Antagonists include:
- Moldy sweet clover
- bishydroxycoumarin
- Rodenticides
- Coumarins (warfarin) or Indanediones (bromadiolone)
- Sulfaquinoxaline and other drugs
- Moldy sweet clover
- Vit K deficiency can also be induced by :
- Anorexia
- Enteric antimicrobials
- Decreased fat digestion or absorption
- Malabsorption
- Cholestasis
- Pancreatic insufficiency
Increased Utilization
- Widespread endothelial injury
- Severe trauma or burns
- Disseminated Intravascular Coagulation
Disseminated Intravascular Coagulation
- a profound disruption of hemostais
- Major stimulu is widespread (systemic) vascular injury
- can occur as a primary event
- infectious agents or toxins that cause widespread vscular injury
- Commonly occurs as a terminal event in shock
- can occur as a primary event
- Causes:
- Necrosis
- Heat stroke
- Neoplasia
- Endotoxemia/spticemia
- Pancreatitis
- Hepatic disease
- Venoms
- trauma
- Burns
- Fundamental change is accelerated o unbalaned cagulation
- elevated levels of both procoagulant and fibrinolytic substances
- Thrombin play a central role in DIC
- activates platelets and coagulation factors
- Activates fibrinolysis
- Widespread nature of the response results in rapid consumption of hemostatic proteins
- consumption coagulopathy
- Widespread, uncontrolled hemorrhage occurs in later stages
- There are inadequate platelet or coagulation factors available to seal up the injured areas
- There are increased levels of FDPs and other degradation products
DIC Morphology
- There are subclinical to severe hemorrhages
- Often large, widespread hemorrhages
- Shock
- Organ failure
- due to thromboembolism or hemorrhage
DIC Significance
- DIC is life-threatening and rapidly progressing event
- one of the most dramatic examples of dyshomeostasis in animals
Hemorrhage
- Loss of blood from the vessel into extravascular sites
- Causes:
- Vascular injury
- Platelet disorders
- Coagulation disorders
Causes of Vascular Injury
- Trauma
- Inflammation (Vasculitis)
- Infectious (Bacteria, viruses)
- Non-infectious (Immune-mediated)
- Secondary invasion
- Inflammatory or neoplastic
- Necrosis
- Toxins
- Infectious agents (viruses)
- Endthelial degeneration
- Endotoxin
Causes of Platelet disorders
- Platelet deficency (thrombocytopenia)
- Decreaed production
- bone marrow injury or supperession
- Excessive utlization
- Widespread injury or DIC
- Premature destruction
- Damage due to viruses or other infectious agents
- Immune-mediated
- Decreaed production
- Abnormal Platelet function (Thrombocytopathy)
Causes of Coagulation Disorders
- Inherited deficiency of coagulation factors
- Acquired coagulation defects
- Decreased production due to liver disease
- Vitamin K antagonism or deficiency
- Rodenticides, sweet clover poisoning, biliary or bowel disease
- Increased use (consumption; DIC)
- Inhibition of coagulation factors
- Heparin, FDPs, antiphospholigpid antibody, antibody to coagulation factors
What is the Pahogenesis of hemorrhages?
- By rhexis:
- Active blood loss due to tears of rents in the blood vessel
- By diapedesis:
- Passive blood loss through endothelial gaps
What is the Morphology of Hemorrages?
- Red irregular foci in tissues characterized by extravascular erythrocytes
How are hemorrhages classified?
- Petechia
- Ecchymosis
- Suffusive
What is the morphology of petechia hemorrhages
- Pinpoint (1-2 mm) hemorrhage usually associeated with mild injury and diapedesis
What is the morphology of Eccymsis hemorrhage?
- Medium (2-3cm) hemorrhage associated with more sever vascular injury
What is the morphology of suffusive hemorrhage?
- Paint brush
- large localized hemorrhage
How do you name hemorrhages into body cavities?
Based on cavity
- Hemopericardium
- Hemothorax
- Hemoperitoneum
What is a hematoma?
- hemorrhage into tissue or interstitium
- extravascular coagulum of blood
What is the significance of hemorrhage?
- Can be insignificant to lig-threatening
What Factors influence clinical outcomes of hemorrhages?
- Location:
- vital vs. non-vital tissues or organs
- Volume:
- Loss of large blood volumes can lead to shock
- Rate of Loss:
- Slow rates of loss can have some compensation
What is a Thrombosis?
- The formation of a solid mass of blood componentss within a blood vessel or the heart
- A reflection of excessive or inppropriate hemostasis
What causes Thrombosis?
- A shift in normal hemostatic balance towards thrombosis
- Endothelial activation/injury
- Platelet activation
- Coagulation pathways activated
- Stasis
- Decreased fibrinolysis
- Abnormal anti-coagulant proteins
What is Virchows Triad?
- Alterations in blood vessels
- Alterations in blood flow
- Alterations in blood coagulability
Cause of Thrombosis
What are some alterations in blood vessels that lead to Thrombosis?
- Endothelial injury
- Trauma
- Chemical injury
- Drugs
- inflammatino
- Immune reactions
- Toxins
Why do thrombi not form normally in blood vessels?
- Normal endothelium is anti-thrombotic
- platelets do not dhere and coagulation is not activated
What causes endothelial injury?
- Viruses (Ex: Canine adenovirus-1)
- Bacteria (Ex: Salmonell)
- Fungi (Ex: Aspergillus)
- Nematode Parasites (Ex: Dirofilaria)
- Immune-mediated vasculitis
- Endotoxin
- Vitamin E/Selenium deficiency
- DIC
What changes in blood flow can lead to the formation of Thrombi?
- Decreased blood flow or stasis
- inceased blood viscosity
- increased endothelium/blood component interactions
- Decreased clearance of activated factors
- Decreased local tissue oxygenation
- Turbulent blood flow
- Enhanves endothelial/blood component interactions
What can cause altered blood flow?
- Gastrointestinal displacement
- gastric or intestinal dilation and volvulus
- Cardiac disease
- Aneurysm
- Strongylus vulgaris
- Hypovolemia
- shock, diarrhea
How does alteration in bood cogulability lead to formation of thrombi?
- Hypercoagulability reflects an increase or decrease in concentrations of activaed hemostatic proteins
- Coagulatino factors or coagulation inhibitors
- This most commonly occurs due to increased activation or decreased degradation of pro-cogulant factors
- Enhanved platelet activity can also contribure
What can cause Hypercogulability?
- Antithrombin deficiency
- Hepatic disease
- Pregnancy
- Nephrotic syndrome/uremia
- Anti-phospholipid antibodies
- Endocrine disease
- Diabetes mellitus, hyperadrenocorticism, hypothyroidism
- Neoplasia
How does Antithrombin deficieny cause alteration in blood coagulability?
- Results in a pro-thrombotic state
- Decreased inactivation of activated factors
- Causes of dificiency include decreased production due to liver disease, increased loss due to liver disease, increased loss due to renal disease or enteropathy (protein-losing nephropathy or enteropathy)
What are the categories of Thombi?
- Arterial Thrombi
- Form in arteries in association with rapidly flowing blood
- Venour Thrombi
- Form in veins in association with slow moving blood
- Cardiac Thrombi
- Form in the hear chambers or on the heart valves
What is the morphology of Arterial Thrombi
- Generally pale and firm
- Consist of alternating layers of fibrin and platelts
- RBCs are washed away due to rapid blood flow
- Ofent have a head (attached to endothelium) and a tail that gros downstream

What is the morphology of Venous Thrombi?
- Dark red, gelatinous
- Consist of fibrin and platelets intermixed with erythrocytes
- Often occclusiveand grow upstream from the point of origin
- Look similar to a postmortem clot

What is the morphology of Cardiac Thrombi?
- Mural cardiac thrombi form in the heat chambers
- Often mold to the outline of the chamber
- Valvular cardiac thrombi from on teh heart valves
- Pale and irregular
- Often associated with infction of the valve

What are the outcomes of Thrombi?
- Lysis
- propogation and Obstruction
- Embolism
- organization
What happens when a thrombus is lysed?
- The thrombus is removed by the dissolution of the fibrin matrix (fibrinolysis)
- Plasmin is a major participantin the process
- This is most common and efficient with new or small thrombi
- Large more mature thrombi are not easily lysed
What happens during propagation ad obstruction with a thrombus?
- The Thrombus grows until ist obstructs teh vessel lumen
- Most common with Venous thrombi
- rapid blood flow past arterial thrombi makes total obstruction more difficult, particularly in larger vessels
- Dependent tissue is often depreived of oxygen

What is an Embolism?
- Embolism occurs when a thrombus or portion of a thrombus breaks loose into the circulation and lodges into another blood vessel
- This can occur with arterial, venous, and cardiac thrombi
- The embolus can damage and occlude the vessel that it lodges within
What is Thrombus organization?
- The process of resolution and healing for large thrombi that cn not be lysed
- Organization reduces the size of the thrombus and converts it to a fibrous scar
Describe the process of Thrombus Organization
- Endothelium grows over teh surface of the thrombus
- Capillaries grow into the thrombus at its point of attachment
- Macrophages and gicroblasts enter the site to remove debris and produce collagen
- New blood vessels can grow into and through the organizing mass (recanalization)

What is the significance of a thrombus?
- The most significant result of a thrombosis is ischemia and infarction
- Thrombi are the most common cause of infarction
- Clincal significance of thrombi depend on their size, location, and type
- Large thrombi tend to be occlusive and more serious
- Thrombi in tissues with poor collateral circulation are more serious
- Venous thrombi tend to be occlusive
