Term
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Definition
| process by which bleeding is stopped |
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Term
| Hemostatis involves a complex interaction between: |
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Definition
1. blood vessels
2. platelets
3. plasma proteins (e.g. coagulation factors)
*Also, contributions from other cellular components of the blood (e.g. monocytes) are being recognized as important factors in hemostatic function in vivo |
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Term
| Description of primary hemostasis |
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Definition
| -initial hemostasis involving activation and formation of platelet plug |
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Term
| Describe clinical signs associated with primary hemostasis. |
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Definition
| petechia, ecchymoses, bleeding from mucosal sites (i.e. gingival bleeding, hematuria, epistaxis, GI bleeding) and proloned bleeding from injection sites |
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Term
| Description of secondary hemostasis |
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Definition
| hemostasis involving coagulation cascade and formation of a fibrin clot |
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Term
| Describe clinical signs associated with secondary hemostasis. |
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Definition
| hematomas, bleeding into joints, body cavities (e.g. abdominal and thoracic cavities) and muscle |
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Term
| Disorder of hemostasis can result in: |
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Definition
-hypocoagulation (hemorrhage) or
-hypercoagulation (thromboembolic disease) |
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Term
| Mammalian platelets are produced by ____________found primarily in the __________. |
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Definition
-megakaryocytes
-bone marrow
*platelets are actually small cytoplasmic fragments of these cells released into circulation. |
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Term
| What do megakaryocytes look like under the microscope? |
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Definition
| -large cells with multilobulated nuclei |
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Term
| What is the primary stimulus for platelet production and where is it produced? |
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Definition
-thrombopoietin
-constantly being produced in liver (also renal tubular epithelium and bone marrow stromal cells) |
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Term
| How is thrombopoeitin cleared? |
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Definition
By receptor-mediated uptake by platelets and megakaryocytes (tends to be an inverse relationship between platelet mass and free TPO)
-as platelet numbers decreased in the peripheral blood, less TPO is cleared from circulation leaving it available to stimulate megakaryocytes to produce more platelets. |
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Term
| Platelet life span is how long? |
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Definition
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Term
| Blood platelet concentration is dictated by: |
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Definition
1. production
2. consumption
3. destruction
4. redistribution
*pathologic states can affect one or more of these factors |
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Term
| Describe platelet morphology/composition. |
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Definition
-relatively small (i.e. smaller than RBC's), anucleate, and generally discoid
-composed of phospholipid bilayer (contains several glycoprotein receptors that function in processes of platelet activation and adhesion) |
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Term
| Platelets contain receptors fro molecules such as: |
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Definition
-fibrinogen
-von Willebrand factor
-collagen
-ADP |
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Term
| What are the two types of granules that platelets contain? |
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Definition
1. alpha granules (contain coagulation and growth factors)
2. dense granules (contain ADP, Ca2+, serotonin) |
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Term
| What happens when platelets are activated by things such as exposure to subendothelial collagen, platelet activating factor, inflammatory mediators, etc.? |
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Definition
| they undergo a general series of reactions as a part of their hemostatic role |
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Term
| Additional importance of platelets: |
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Definition
| Important in inflammatory processes Platelets are important in inflammatory process (e.g. elaboration of cytokines, interaction with leukocytes, activated by infectious agents), maintenance of vascular integrity, and tissue repair. |
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Term
| Laboratory evaluation: platelet concentration |
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Definition
-generally performed on an automated analyzer as part of a CBC
-evaluation of blood smear is still important to evaluate platelet clumps |
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Term
| How can platelet clumps impact the platelet concentration from the automated analyzer? |
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Definition
-If clumps are present, platelet concentration from automated analyzer can be interpreted as a minimum
-If platelet clumps are present, some labs report as "adequate"
- |
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Term
| What is the minimum normal platelet estimate (performed on a 100x objective)? |
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Definition
| -(8-10) platelets/100 x field |
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Term
| Why are feline platelet concentrations often somewhat inaccurate and relatively low? |
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Definition
| -due to tendency to form platelet clumps and relatively large platelet size (i.e larger platelets may be counted as RBCs on some analyzers) |
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Term
| Hemorrhage from thrombocytopenia is often not noted until platelet concentration is less than what value: |
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Definition
<25,000 /uL
*Note: when animals bleed due to low platelet numbers it is largely the result of platelets role in the maintenance of vascular integrity as well in hemostasis |
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Term
| What process should be considered if hemorrhage is occurring at higher platelet concentrations (i.e.> 50,000/uL)? |
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Definition
| -platelet function defect or DIC |
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Term
| Presence of macroplateletes is noted on the morphology section of a CBC. What are these large platelets often released in response to? What do they indicate? |
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Definition
| -released form bone marrow in response to thrombocytopenia and are an indicator of bone marrow regeneration or response |
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Term
| Macroplatelets appear to be hyperfunctional. What is a consequence of this? |
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Definition
| Some animals with relatively low platelet concentrations do not bleed if many of the platelets are macroplatelets |
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Term
| What affect with significant numbers of macroplatelets have on MPV? |
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Definition
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Term
| List the laboratory tests use to evaluate platelets. |
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Definition
1. platelet concentration
2. platelet morphology
3. mean platelet volume (MPV)
4. platelet distribution width (PDW)
5. Buccal Mucosal Bleeding Time (BMBT)
6. Others: Antiplatelet antibody, antimegakaryocyte antibody, platelet aggregometry, plateletcrit, platelet function analyzers |
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Term
| Characteristics of platelet distribution width (PDW) |
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Definition
-coeffiecient of variation of platelet volume (essentially a measure of the variability in platelet volume)
-increased numbers of large and/or small platelets will increase PDW |
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Term
| Characteristics of Buccal Mucosal Bleeding Time (BMBT) |
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Definition
| -performed by creating a small standardized incision in buccal mucosa or gingiva and measuring time it takes for bleeding to cease (i.e. formation of platelet plug) |
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Term
| What can cause increased BMBT? |
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Definition
-moderate to marked thrombocytopenia
-inherited or acquired platelet function defects
-vascular abnormalities
(Coagulation factor abnormalities will not prolong BMBT |
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Term
| BMBT is most appropriately used to evaluate _____________when _____________numbers of platelets are present. |
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Definition
-platelet function
-relatively normal |
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Term
| List mechanisms of thrombocytopenia: |
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Definition
1. increased platelet destruction/consumption
2. Decreased platelet production
3. abnormal platelet distribution
4. multifactorial
5. idiopathic |
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Term
| List mechanisms of increased platelet destruction/consumption (causing thrombocytopenia). |
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Definition
1. Immune-mediated thrombocytopenia (ITP)
2. Vasculitis
3. DIC
4. Blood loss (mild to moderate blood loss alone usually doesn't cause a significant thrombocytopenia; severe, acute blood loss can occasionally result in a mild to moderate thrombocytopenia) |
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Term
| Describe immune-mediated thrombocytopenia (ITP) |
|
Definition
-common cause of marked thrombocytopenia in dogs (usually <50,000/uL and often <10,000/uL)
-antibody-mediated destruction of platelets
-may be primary (i.e. idiopathic) and directed at "normal" antigens on platelet surface or seconday (e.g. drugs, infectious organisms, neoplasia, neonatal alloimmune thrombocytopenia) |
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Term
| Describe vasculitis as a cause of thrombocytopenia. |
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Definition
-exposure of subendothelium leads to prothrombic state
-vasculitis can have infectious (e.g. RMSF, immune-mediated, physical, and chamical causes) |
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Term
| Describe DIC as a cause of thrombocytopenia |
|
Definition
-systemic uncontrolled activation of coagulation
-ALWAYS SECONDARY to underlying pathologic processes (e.g. neoplasia, sepsis, toxicosis, heat stroke, heartworm, immune-mediated dz)
-usually results in mild to moderate decreases in platelet concentration (animals may bleed, however, due to concurrent abnormalities with secondary hemostasis and/or platelet dysfunction)
-Note: subclinical DIC or localized intravascular coagulation can occur resulting in thrombocytopenia |
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Term
| List decreased platelet prouduction causes of thrombocytopenia. |
|
Definition
1. aplastic pancytopenia
2. Generalized bone marrow replacement or damage
3. Immune-mediated destruction of megakaryocytic precursors (megakaryocytic hypoplasia/aplasia) |
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Term
| Describe aplastic pancytopenia (a decreased platelet production cause of thrombocytopenia). |
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Definition
| -causes such as estrogens, chemotherapeutic agents, bracken fern poisoning (ruminants), mycotoxins, etc. |
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Term
| Describe generalized bone marrow replacement or damage (a decreased platelet production cause of thrombocytopenia). |
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Definition
| -myelophthisis, myelofibrosis, myelonecrosis, irradiation |
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Term
| Describe immune-mediated destruction of megakaryocytic precursors (megakaryotic hypoplasia/aplasia) a decreased platelet production cause of thrombocytopenia. |
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Definition
-rare disorder
-antibodies directed at megakaryocytes and their precursors in the bone marrow |
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Term
| Abnormal platelet distrubution can cause thrombocytopenia. Splenic congestion or splenomegaly of this mechanism. Describe splenic congestion or splenomegaly. |
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Definition
| -may cause "pooling" or platelets in the spleen, contributing to and rarely, by itself, causing significant thrombocytopenia |
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Term
| List multifactorial causes of thrombocytopenia. |
|
Definition
1. neoplasia-relatively common; many types of neoplasias are associated with thrombocytopenia; mechanisms include: decreased production (e.g. myelophthisis), increased consumption (ie. DIC) and possibly redistribution
2. Infectious agents-i.e. Ehrlichia, Anaplasma; cause thrombocytopenia through multiple mechanisms such as suppressed platelet production (e.g. direct infection of precursors, immune-mediated damage, local effects of marrow inflammation) and increased platelet destruction/consumption (immune and non-immune mediated mechanisms) |
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Term
| Describe Idiopathic thrombocytopenia of Cavalier King Charles Spaniels (an idiopathic mechanism of thrombocytopenia) |
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Definition
-inherited disorder reported to have an autosomal recessive pattern
-disorder is characterized by thrombocytopenia and macrothrombocytosis
-platelet concentrations are often 50-100 X 10^3/uL
-affected animals DO NOT have clinical bleeding problems (thus recognition of this condition is important in context of preventing unnecessary tx and/or misdiagnosis) |
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Term
| List mechanisms for thrombocytosis. |
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Definition
1. increased production
2. redistribution
3. hemic neoplasia |
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Term
| List causes of increased production of platelets (an underlying mechanism for thrombocytosis) |
|
Definition
1. inflammation: inflammatory cytokines (esp. IL-6) stimulate TPO production resulting in increase in thrombopoiesis; can be secondary to infxs, neoplasia, trauma, etc.
2. iron deficiency: common, but inconsistent finding in canine patients; cause not known
3. rebound thrombocytosis: thrombocytopenia can sometimes stimulate enough platelet production that platelet concentrations are transiently elevated (i.e. overcompensation)
4. Vinca alkaloids: stimulate thrombopoiesis
5. Splenectomy: due to increased blood concentrations of TPO, as a large % of total platelet mass is removed with the spleen |
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Term
| Describe exercise and epinephrine (an underlying redistribution mechanism causing thrombocytosis) |
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Definition
| -strenuous exercise and/or epinephrine release can result in mild, transient, physiologic thrombocytosis in some animals (other changes: mature neutrophilia, lymphocytosis, transient change) |
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Term
| Describe hemic neoplasia (an underlying hemic neoplasia mechanism causing thrombocytosis) |
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Definition
| -primary (essential) thrombocytosis: chronic membroproliferative disorder of platelet precursors that results in large numbers of relatively normal platelets |
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Term
|
Definition
-decreased platelet function
-whether inherited or acquired, thrombopathies result from defects or deficiencies in platelet surface receptors, their ligands, or signaling pathways
-clinically, these result in bleeding in spite of normal platelet numbers |
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Term
| List types of thrombopathy |
|
Definition
1. inherited
a. Von Willebrand Disease (vWD)
b.Others: other inherited platelet function defects exist but are beyond the scope of this lecture. Examples: Basset-hound thrombopathy, Thrombasthenia thrombopathy of otterhounds and foxhounds, Chediak-Higashi syndrome, Glanzmann's Thrombathenia
2. Acquired: variable degrees of platelet dysfunction can be secondary to a number of causes such as:
-drugs (esp NSAIDS)
-DIC
-Hepatic dz
-Hyperglobulinemia
-Uremia |
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|
Term
| Von Willebrand Disease (vWD) (most common cause of thrombopathy) |
|
Definition
-most common hereditary bleeding disorder in dogs
-rare in cattle, swine, cats, and horses
-animals have bleeding tendencies in spite of normal platelet numbers and coagulation times |
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Term
| Von Willebrand Factor description: |
|
Definition
-multimeric glycoprotein produced by endothelial cells and megakaryocytes
-vWF bridges platelets to subendothelial collagen and contributes to platelet-platelet bridging/binding
-vWF of different multimeric weights is produced, with largest multimers (i.e. high-molecular weigh) being most functional
-vWF also forms complexes with coagulation factor VIII in circulation and stabilizes this molecule |
|
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Term
|
Definition
1. BMBT (prolonged)-initial diagnostic test
2.confirm with vWF antigen assay and vWF multimeric analysis |
|
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Term
| Describe the three types of vWD: |
|
Definition
1. Type 1 (many breeds including Welsh Corgi and Dobermans). All multimers are decreased. This is the most common type of vWD and has variable severity.
2. Type 2: (German Shorthair Pointers), decreased levels of vWF with a disproportionate decrease in large multimers. This type is uncommon, but severe.
3. Type 3: (Scottish terrier, Chesapeake Bay Retriever, Shetland Sheepdog). Undetectable levels of vWF. Causes severe disease. |
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