Platelets and Platelet Disorders Flashcards
Buccal Mucosal Bleeding Time (BMBT)
Make a standarize incision, blood blood gently and measure time for bleeding to cease
Hemostasis
Stoppage of blood
Thrombocytopenia due to destruction by modified live virus vaccination
May induce an immune response against the platelet → platelet aggregation → clearance
Occurs 3-10 days post vaccination
Avoid surgery
Sequestration of platelets in large vascular beds
Splenomegaly, splenic torsion, neoplasia
Hepatomegaly, portal hypertension
Vasodilation in endotoxic shock
Severe hypothermia
1/3 of platelet mass is in the
Spleen
What is the order of events in platelet plug formation?
Adhesion
Activation
Aggregation
Thrombocytopenia due to destruction can be caused by
Immune mediated thrombocytopenia (ITP)
Alloimmune thrombocytopenia
Laboratory tests used for platelet function
Bleeding time tests
Specific platelet function tests
Bone Marrow Aspirate (BMA)
Evaluate megakaryocyte number and morphology
Secondary or reactive thrombocytosis is associated with
Chronic Inflammatory Disease
Iron Deficiency Anemia
Chronic Hemorrhage
IMHA
Some neoplasms
Clinical signs associated with thrombocytopenia
Platelet bleeding pattern
Bleed from mucosal membranes
Petechiation to ecchymosis
+/- anemia
Cuticle (Toenail) Bleeding Time
Use a guillotine clipper and sever apex of nail, blot blood gently, and measure time for bleeding to stop
Pseudothrombocytopenia occurs because
Analyzer does not measure platelets because they are too big or clumped
Clot retraction and inflammation are involved in
Secondary Hemostasis
vWF is carrier for
Factor VIII
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Severe disease, may also have factor VIII deficiency
Vascular Injury causes:
Vasoconstriction
Activation of hemostasis
Platelets
Coagulation Factors
Major mechanisms of thrombocytosis
Increased production
Increased distribution in plasma
Two forms of von WIllebrand Disease (vWD)
Quantitative Deficiency (Type 1 and 3)
Qualitative abnormality (Type 2)
Granulation products secreted during the activation phase of primary hemostasis
Factors V and VIII
Thromboxane A2
Calcium
ADP
vWF
Thrombocytopenia due to decrease production can be the cause of
Bone marrow hypoplasia
Neoplasia
Myelonecrosis or myelofibrosis
Life span of platelets
5-10 days
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Shorter in cats
Megakaryocytes
Large Cells
Polyploid nucleus
Abundant cytoplasm
Hemostasis requires the interaction of
Blood Vessels
Platelets
Coagulation Factors
Increased numbers of enlarged platelets suggests
Active production of platelets
Laboratory tests used for platelet concentration and morphology
Blood smear
Hematology analyzers
Bleeding Tests
Tests the ability of platelets to form a platelet plug - does not test fibrin plug formation
Clot Retraction occurs via
Actinomyosin filaments
Von Willebrand Factor (vWF)
Binds to GPIb on platelet surface
Bridge between platelet and collagen
Immunofluorescent Antimegakaryocytic Antibody Test
Detects antibodies on megakaryocytes
Hemostasis is a balance between
Thrombus and hemorrhage
Laboratory test used to evaluate anti-platelet antibodies
Platelet Surface-Associated Immunoglobulin (PSAIg)
Immunofluorescent Antimegakaryocytic Antibody Test
Thrombus causes
Increased procoagulant activity or decreased fibrinolysis
Hemorrhage causes
Decreased procoagulant activity
Decreased platelet number or loss of platelet function
Increased fibrinolysis
Clot retraction facilitates
Wound closure
Vessel patency
Bleeding tests are abnormal (prolonged) when:
Decreased platelet function
Decreased platelet numbers
Pathology of thrombus
Excessive thrombus formation → obstructed blood flow → local hypoxia
Maturation time of megakaryoblast to platelets
4-5 days
Increased mean platelet volume (MPV) suggests
Increased thrombopoiesis
Activation phase of primary hemostasis allows for
Recruitment of more platelets
Further platelet activation
Facilitate coagulation
Mediate vessel repair
Clinical features of thrombocytopenia
Mucosal bleeding
Petechiation
Ecchymosis
Spontaneous hemorrhage
+/- hemorrhagic anemia
Primary Hemostasis
Formation of a primary hemostatic plug
Take 3-5 minutes
- Platelets adhere to subendothelium
- Undergo activation
- Aggregate to form a platelet plug
Aggregation phase of primary hemostasis
Irreversible
Mediated by ADP, Thromboxane A2
Thrombin = positive feedback
Ca required
Acquired cause of qualitative platelet disorders
Uremia
Drugs
Fibrin Degradation Products (FDPs)
Paraproteins
Increased concentration platelets associated with what situations
Rebound from thrombocytopenia
Response to some drugs
Post splenectomy
Excitment and exercise
Splenic contraction
Secondary Hemostasis
Surface for formation and deposition of fibrin
Occurs on the platelet surface
Describe the activation step of primary hemostasis
- Shape change - smooth discs to spheres with filopoida in response to thrombin
- Flip membrane - negative charge on outer membrane of platelet
- Secretion of granule products
Fibrin Degradation Products (FDPs) cause aquired qualitative platelet disorders by
Inhibiting platelet function in disease processes
Von Willebrand Disease (vWD)
No defects in platelets
Defect is in the adhesion molecule that binds platelets during initaition of platelet plug
Decreased platelet adhesion
Mechanisms of thrombocytopenia
Decreased production
Destruction
Sequestration
Loss
Consumption
Pseudothrombocytopenia
Thrombopoietin (TPO)
(+) Megakaryocyte production and differentiation
Continually produced by liver, bone marrow, endothelium, etc
Binds to receptors on platelets
Inherited qualitative platelet disorders
Absence of glycoprotein receptors
Absence or reduction in platelet granules
Signal transduction defects
Von Willebrands Disease
Suspect qualitative platelet disorder in an animal with
Clinical signs of thrombocytopenia
Normal platelet count
Thrombocytopenia due to abnormal distribution of platelets
Seqestration of platelets in large vascular beds
Thrombocytosis
Platelet count greater than upper reference interval
Platelet Surface Associated Immunoglobuin (PSAIg)
Difficult to perform because platelets normally carry some immunoglobulin
Laboratory tests for thrombocytopenia
Complete blood count (CBC) - severe thrombocytopenia
Other coag tests - PT, PTT will be normal
Bone marrow aspirate - increased megakaryocytes
Anti-platelet Antibody Tests - positive
Serum biochemistry - normal
Alloimmune Thrombocytopenia
Dam produces antiplatelet antibody from a previous pregnancy
Offspring ingests antibody in the colostrum
Alpha2Beta1 (GP Ia - IIa) and GP VI Receptors
Bind platelets directly to collagen
Initiate intracellular signaling → activation, adhesion
Pathology of hemorrhage
Inability to form a thrombus → hemorrhage
Thrombocytopenia
Platelet count less than lower reference interval
Action of TPO on the bone marrow
Increase number, size and ploidy of megakaryocytes
Decreased megakaryocyte maturation time
Laboratory test used for platelet production evaluation
Bone marrow aspirate (BMA)
Clinical features of von Willebrand Disease
Mild to severe bleeding
Exacerbated by surgery or trauma
Signs decrease with age and successive pregnanacies
Describe the morphology of platelets
Small granular discs
Membrane glycoproteins - receptors for ligands
Anucleate
Cytoskeleton
Alpha and dense granules
Canalicular and tubular systems
Laboratory tests of von Willebrand Disease
Platelet count - normal
BMBT - prolonged
PTT/ACT - normal, but can be prolonged if Factor VIII deficient
Beta1-tubulin gene mutation
CKCS
Point mutation
Alters cytoskeleton
Causes mactrothrombocytes - decreased platelets, increase platelet MCV
Usually asymptomatic
Thrombocytopenia due to consumption can be caused by
Disseminated intravascular coagulation (DIC)
Vasculitis
Viral infection
Macroplatelets are suggestive of
Increased platelet production
Paraproteins cause aquired qualitative platelet disorders
Plasma cell myeloma → increased globulins coat platelet surface and inhibit function
Regulation of thrombopoiesis by
Thrombopoietin (TPO)
