Platelets Flashcards
List characteristics of platelet morphology
Small granular discs Membrane glycoproteins that act as receptors for ligands (vWF and fibrinogen) Anucleate Cytoskeleton alpha and dense granules canalicular and tubular systems
What is the lifespan of a platelet?
5-10 days
Where is 1/3 of platelets located?
spleen
What are the presence of macroplatelets suggestive of?
increased platelet production
What is the precursor to platelets?
Megakaryocytes
What regulates megakaryocyte production and differentiation?
Thrombopoietin
What happens when there are decreased numbers of platelets?
free plasma TPO increases –> Bone marrow –> increase in number, size and ploidy of megakaryocytes
What do you use to test Platelet concentration and morphology?
Blood smear
Hematology analyzer
What do you use to test function of platelets?
Bleeding time tests
Specific platelet function tests
What do you use to test production of platelets?
Bone marrow aspirate
What do you use to test anti-platelet antibodies?
Platelet surface assocaited immunoglobulin (PSAIg)
Immunofluorescent antimegakaryocytic antibody test
Below what interval is Thrombocytopenia severe?
Below what interval would you have spontaneous hemorrhage?
What does MPV stand for?
Mean Platelet Volume
What does an increased MPV suggest?
increased thrombopoiesis
What does an increased number of enlarged platelets suggest?
active production of platelets
In thrombocytopenia, free TPO should be….
Increased
If TPO is increased and the bone marrow is healthy, you expect to see…
Increased megakaryocyte numbers with increased ploidy
What 3 things suggest platelet regeneration?
Macroplatelets on theh blood smear
Increased MPV
Increased megakaryocyte numbers
What are you evaluating on a bone marrow aspirate?
megakaryocyte number and morphology
A prolonged BMBT (Buccal mucosal bleeding time) can be caused by:
decreased number of platelets
What are the Clinical features of Thrombocytopenia?
Mucosal bleeding Petechiation Ecchymosis Spontanous hemorrhage hemorrhagic anemia
What are the mechanisms of Thrombocytopenia?
Production Destruction Sequestration Loss Consumption
What is the mechanism for decreased production?
Bone marrow hypoplasia
Neoplasia
Myelonecrosis or Myelofibrosis
The degree of thrombocytopenia depends on….
the extent of bone marrow disease
What is the mechanism for destruction of platelets?
Immune mediated thrombocytopenia
Alloimmune thrombocytopenia
Modified live vaccination
What is Alloimmune thrombocytopenia?
Dam produces antiplatelet antibodies from previous pregnancy
What are the two types of immune mediated thrombocytopenia?
Primary
Seconday
What is primary immune mediated thrombocytopenia?
Idiopathic
What is secondary immune mediated thrombocytopenia?
Drugs
Viruses
Sepsis
Neoplasia
How does a modified live vaccination cause thrombocytopenia?
Induces an immune response against platelets –> platelet aggregation –> clearance
What are the clinical signs for destructive thrombocytopenia?
Bleeding from the mucosal membranes
petechiation
Ecchymosis
+/- anemia
Platelet counts in patients with immune mediated thrombocytopenia are typically…
Severely decreased
What kind of thrombocytopenia will you see with sequestration of platelets?
Mild to moderate thrombocytopenia
When you would you see sequestration of platelets?
Splenomegaly Splenic torsion neoplasia Hepatomegaly portal hypertension vasodilation in endotoxic shock severe hypothermia
What kind of thrombocytopenia would you see with hemorrhage?
Normal to Mild thrombocytopenia
What causes consumption of platelets?
DIC
Vasculitis
Viral infection
When does pseudothrombocytopenia happen?
Macroplatelets
Clumped platelets
On a blood smear marked macrothrombocytosis is observed. This finding correlates with:
Increased MPV
What is thrombocytosis?
Increased concentration of platelets
What are the 2 major mechanisms of thrombocytosis?
Increased production
Increased distribution in plasma
what is a primary cause of Thrombocytosis?
Neoplasia
What is a secondary cause of thrombocytosis?
Chronic inflammatory disease
Iron deficiency anemia
Chronic hemorrhage
IMHA
What other causes can cause thrombocytosis?
Rebound from thrombocytopenia Response to some drugs Post-splenectomy Excitment and exercise Splenic contraction
Hemostasis
Stoppage of blood
What causes the formation of a thrombus?
increase procoagulant activity
decreased fibrinolysis
What causes hemorrhage?
decreased procoagulant activity
decreassed platelet number or loss of platelet function
Increased fibrinolysis
What is primary hemostasis?
the formation of a primary hemostatic plug
What are the steps of Primary Hemostasis?
Adherence –> Activation –> Aggregation
What factor is used to bind GP1b to platelet surface?
von Willebrands Factor
What are the factors required for activating the platelet?
Calcium
ADP
Thromboxane A2
Thrombin
What happens to the platelet during activation?
A shape change
flipping of the membrane
spreading out to create more surface area
What happens when Phosphotidylserine flips to the outside of the platelet membrane?
The surface becomes negatively charged
What happens during activation?
Platelet plug is formed
What else do platelets do to aid in regeneration and repair?
They retract to pull the edges of the wound together
What do bleeding tests test for?
The ability of platelets to form a platelet plug
When is bleeding time abnormal or prolonged?
Decreased platelet function
decreased platelet numbers
What diagnostic test is commonly used to assess platelet function?
Buccal mucosal bleeding time (BMBT)
When do you suspect a qualitative disorder in an animal?
Clinical signs of thrombocytopenia
Normal Platelet count
What are the two types of qualitative disorders?
Acquired
Inherited
What can cause an acquired qualitative disease?
Uremia
Drugs
Fibrin degradation products
Paraproteins
What can cause an inherited qualitative disorder?
Absence of glycoprotein receptors
Absence or reduction in platelet granules
Signal transduction defects
Von Willebrand disease
von Willebrand Disease
Defects in the adhesion molecule that binds platelets during initiation of platelet plug causing decreased platelet adhesion
vWF is a carrier for….
Factor VIII
What are the two forms of von Willebrand disease?
Quantitative deficiency
Qualitative abnormality
What are the clinical signs of von Willebrands disease?
Mild to severe bleeding
When do signs decrease for von Willebrands disease?
with age and successive pregnancies
When do you suspect von Willebrands disease?
Platelet count is normal
Buccal mucosal bleeding time is prolonged
What is secondary hemostasis?
Stabilization of the platelet plug via fibrin meshwork
Which Factor is involved in the extrinsic pathway?
Factor VII
Which Factors are involved in the Intrinsic pathway?
Factor XII, XI, IX, VIII ( Not $12 but $11.98!)
What factor is Calcium?
Factor IV
Where are coagulation factors synthesized?
Liver
What are the two types of factors involved in the coagulation cascade?
Enzymatic and Nonenzymatic
What converts Fibrinogen to Fibrin?
Thrombin
What converts Prothrombin to Thrombin?
Factor Xa with Factor Va
What two factors convert Factor X to Xa?
Factors IXa, VIIa, and VII with the help of Factor VIIIa
What converts Factor VII to VIIa?
Tissue Factor (III) Factor Xa
What converts Factor IX to IXa?
Factor VIIa
What conversions is Tissue Factor (III) involved in?
Factor VII –> VIIa
Factor IX –> IXa
What conversions is Factor Va involved in?
Prothrombin to Thrombin
What three phases are the cells involved with the coagulation cascade?
Initiation
Amplification
Propagation
What is required for the initiation of secondary hemostasis?
Tissue Factor (III)
What does thrombin promote?
Amplification
How does Thrombin promote amplification?
By feedbacking to Factors: XI, VII, VIIIa, and Va
What is propagation?
Thrombin is generated on the platelet surfce driving formation of Fibrin
What inhibits Thrombin, Factor IXa and Xa?
Antithrombin
How does Antithrombin work?
Heparin binds to Antithrombin –> Heparin causes conformationa; change and exposes the thrombin binding site –> Thrommbin binds to AT=TAT complex and Heparin floats away –> the TAT complex is cleared by the phagocytic system
What is formed when there is excess fibrin production?
Schistocytes
What else helps break down Fibrin?
Plasminogen secreted by neighboring cells –> converted to Plasmin byttissue Plasminogen Activator (TPA)
What three things does Plasmin act on?
Fibrinogen
Soluble Fibrin
Cross linked fibrin
What is created when plasmin acts on soluble fibrin?
Fibrin Degradation Products
What is created when plasmin acts on cross-linked fibrin?
D-Dimers
What tests can test for Procoagulant activity?
Activated Partial Prothrombin time (aPTT, PTT) Prothrombin time (PT) Thrombin Time (TT), Fibrinogen PIVKA Specific factor assays
What tests can test for anticoagulant activity?
Fibrinolytic activity - Fibrin degradation products, D-Dimers Inhibitor consumption (Antithrombin (AT))
What tube do you use for plasma testing?
Blue top Sodium Citrate Tube
What two tests are used for the Intrinsic pathway?
aPTT
ACT
What test is used for the extrinsic pathway?
PT
What tests for Fibrinogen?
TT
What does aPTT stands for?
Activated partial thromboplastin time
What does ACT stand for?
Activated Clotting Time
What are the aPTT and ACT testing for?
Measure time for Fibrin clot formation
What is the significance of a prolonged aPTT or ACT?
Deficiency or inhibition of any intrinsic or common pathway factor
Heparin Therapy
What percent deficiency of factor is required before prolongation is detected in aPTT?
70%
What percent deficiency of factor is required before prologation is detected in ACT?
95%
What is the significance of prolongation in a PT?
Factor VII deficiency (Good screening for Vitamin K deficiency)
Deficiency or inhibition of common pathway factor
What percent deficiency of factor is required before prolongation is detected in PT?
70%
When does increased concentration of Fibrin Degradation products occur?
Increased Fibrinolysis
Severe internal hemorrhage with fibrinolysis
Decreased clearnace of FDP by liver
When does increased concentration of D-Dimers occur?
Increased fibrinolysis
Severe internal hemorrhage with fibrinolysis
Decreased clearance of FDP by the liver
What causes Warfarin Toxicosis?
Poisoning with coumarin derivatives
How does Warfarin interfere with the clotting cascade?
It inhibits the Vitamin K cycle causing the Factors to not become negatively charged and therefore not attracted to platelets
What are the clinical signs of Warfarin Toxicosis?
Bleeding
Anemia
Hypovolemic shock
Dyspnea due to bleeding into the thoracic cavity
Lameness due to bleeding into the joints
Neurological signs due to bleed in the brain
What are the laboratory features of Warfarin Toxicosis?
Regenerative Anemia Variable Leukogram Normal Platelet count Prolonged PT, aPTT, ACT Positive PIVKA
What is the treatment for Warfarin Toxicosis?
Decontamination
Supplement Vitamin K
Plasma and/or blood transfusions
What is DIC?
Disseminated Intravascular Coagulation - Depletion of the coagulation factors and platelets –> bleeding
What is the cause of DIC?
continued activation of coagulation and fibrinolysis - Sepsis Tissue Necrosis Neoplasia Proteolytic Enzymes (Snake venom) Stagnant blood flow
What are the two phases of DIC?
Hypercoagulable
Consumptive
What happens in the Hypercoagulable phase of DIC?
Thrombosis
Ischemic necorsis and organ dysfunction
What happens in the consumptive phase of DIC?
Consumption of platelets, coag factors, and AT
Bleeding!!
What are the clinical signs associated with DIC?
Signs of Organ Dysfunction
Bleeding - Mucosal and Hemorrhage
What are the laboratory features of the consumptive phase of DIC?
Thrombocytopenia Prolonged PT, aPTT Decreased fibrinogen concentration increased FDP and D-dimers Decreased antithrombin (AT) Hemorrhagic anemia Schistocytes
What is the treatment for DIC?
Identify and eliminate the underlying disorder
Fluid therapy
Transfusion therapy
What is the cardinal bloodwork finding for a patient in the consumptive phase of DIC?
Thrombocytopenia
What is coagulopathy and liver disease?
decreased synthesis of coagulation factors
Production of dysfunctional factors
What is a inherited factor deficiency?
Hemophilia A: VIII
What are the clinical signs of hemophilia A: VIII?
Mild, moderate, or severe bleeding
What are the laboratory findings for Hemophilia A: VIII?
Normal Platelet count
Prolonged aPTT and ACT
PT is normal
What kind of genetic disorder is Hemophilia A: VIII?
X-linked recessive in dogs and cattle
