Abnormal Hemostasis Flashcards
(60 cards)
1
Q
Abnorma Hemostasis
A
Inadequate hemostasis can lead to hemorrhage
Excessive or inappropriate hemostasis can lead to thrombosis
2
Q
Platelet Diorders:
A
- Platelet deficiency:
- decreased production
- excessive utilization
- premature destruction
- Abnormal platelet function (Thrombocytopathy)
3
Q
Decreased Platelet Numbers
A
- Adequate numbers of platelets are necessary for successful response to vascular injury
4
Q
Causes of Thrombocytopenia:
Decreased Production
A
- Myelophthesis
- Bone marrow neoplasia myelofibrosis
- Chemicals:
- Estrogen, bracken fern, trichothecene mycotoxins
- Drugs:
- Chloramphenicol, sulfonamides, phenybutazone
- Radiation and chemotherapy
5
Q
Causes of Thrombocytopenia:
Increased consumption
A
- Endothelial activation:
- Vasculitis, infectious agents.
- localized intravascular coagulation
- vascular neoplasia, hemorrhage, thrombosis
- Disseminated Intravascular Coagulation:
- Endotoxemia, shock
6
Q
Causes of Throbmycytopenia:
Increased Destruction
A
- 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
7
Q
Abnormal Platelet Function
A
- 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
8
Q
Causes of Thrombocytophathy:
Inherited problems of adhesions
A
- 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
9
Q
Von Willebrand Disease
A
- 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
10
Q
Causes of Thrombocytopathy:
Acquired platelet function problems
A
- Drugs
- Uremia assocaited with renal failure
- Increased FDPs
- Hepatic disease
- Immune-mediated thrombocytopenia
- Megakaryocytic neoplasia
- Infection
- BVDV and FeLV
11
Q
Acquired Platelet Dysfunction
A
Antiplatelet drugs:
Aspirin
Irreversible inhibition of the cyclooxygenase pathway of arachidonic acid metabolism in platelets
Thromboxane A2 synthesis is inhibited
12
Q
Coagulation Disorders
A
- 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
13
Q
Causes of Coagulation Disorders
A
- 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:
14
Q
Inherited Coagulation Factor Deficiences:
Hemophilia A
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:
15
Q
Inherited Coagulation Factor Deficiencies:
Intrinsic:
Hemophilia B
A
- Factor IX deficiency, x-linked recessive
- Reported in dogs and cats
- Similar signs to Hemophilia A
- Most cases Factor IX activity is very low
16
Q
Inherited Coagulation Factor Deficiencies:
Intrinsic:
Hemophilia A and B
A
- 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.
17
Q
Acquired Coagulation Disorders
A
- 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
18
Q
Acquired Coagulation Disorders:
Liver Disease
A
- Decreased production of both pro- and anti- coagulation factors
- Bleeding is uncommon unless liver disease is severe or associated with DIC
19
Q
Acquired Coagulation Disorders:
Vitamin K deficiency
A
- Antagonists inhibit conversion of oxidized vitamin K to reduced (Active) form
- These include:
- moldy sweet clover
- Rodenticides
- Sulfaquinoxaline and other drugs
*
20
Q
Acquired Coagulation Disorder:
Increased Utilization
A
Widespread endothelial injury
Severe Trauma or burns
Disseminated Intravascular Coagulation
21
Q
Hemostatic Dyshomeostasis:
Disseminated Intravascular Coagulation
A
- 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
22
Q
Disseminated Intravascular Coagulation
A
- 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
23
Q
DIC:
Morphology
A
There are subclinical to severe hemorrhage
Shock
Organ failure
24
Q
DIC:
significance
A
Is a life-threatening and rapidly progressing event
one of the most dramatic examples of dyshomeostasis in animals
25
Abnormal Hemostasis:
Hemorrhage
the loss of blood from the vessel into extravascular sites
26
Hemorrhage:
Causes
Vascular Injury
Platelet Disorders
Coagulation Disorders
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Causes of Vascular Injury
* Trauma
* Inflammation
* infectious
* non-infectious
* Secondary invasion
* inflammatory or neoplasitc
* Necrosis
* toxins
* Infectious agents
* Endothelial degeneration
* endotoxin (LPS)
28
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)
29
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
30
Hemorrhage:
Pathogensis
* By rhexis:
* Active blood loss due to tears or rents in the blood vessel
* By Diapedesis:
* Passive blood loss through endothelial gaps
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Hemorrhage:
Morphology
* Red irregular foci in tissues characterized by extravascular erythrocytes
* Classification:
* petechia
* Ecchymosis
* Suffusive
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Hemorrhage:
Morphology:
Petechia
pinpoint (1-2mm) hemorrhage usually assocaited with mild injury and diapedesis
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Hemorrhage:
Morphology:
Eccymosis
Medium (2-3cm) hemorrhage assocaited with more severe vascular injury
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Hemorrhage:
Morphology:
Suffusive (Paint Brush)
Large localized hemorrhage
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Hemorrhage:
Morphology:
Into a body cavity
Hemopericardium
Hemothorax
Hemoperitoneum
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Hematoma
Hemorrhage inot tissue or interstitium
An extravascular coagulum of blood
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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
38
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
39
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
40
Thrombosis:
Alterations in blood vessels
* Endothelial injury
* trauma
* Chemical injury
* Drugs
* Inflammation
* Immune reactions
* Toxins
* Normal endothelium is anti-thrombotic
* platelets do not adhere
41
Thrombosis:
Alterations in Blood Vessels:
Endothelial Injury Causes
* Viruses
* Bacteria
* Fungi
* Nematode parasites
* Immune-mediated vasculitis
* Endotoxin
* Vitamin E/selemium
* DIC
42
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
43
Thrombosis:
Alterations in blood flow:
Turbulent Blood Flow
enhances endothelial/blood component interactions
44
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
45
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
46
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
47
Thrombosis:
Arterial Thrombi
These form in arteries in association with rapidly flowing blood
48
Thronbosis:
Venous Thrombi
These form in veins in associates with slow moving blood
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Thrombosis:
Cardiac Thormbi
These form in the heart chambers or on the heart valves
50
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
51
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
52
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
53
Thrombus:
Outcomes
Lysis
Propogation and obstruction
Embolism
Organization
54
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
55
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
56
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
57
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
58
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)
59
Thrombus:
Significance
* Most significant result of thrombosis is ischemia and infarction
* Clinical significance of thrombi depend on their size, location, and type
*
60
Significance:
Infarction
Pulmonary infarction
Renal infarction
