Platelets and Hemostasis Flashcards
Thrombocytosis:
Def
Causes
Def: increased platelets
Causes:
- inflammation (IL-6, TNF-alpha, IL-1) => cause inc thrombopoietin production
- Iron deficiency anemia
- Cushing’s disease 4. Steroid therapy
What doesn’t cause a thrombocytopenia (usually)
hemorrhage bleeding
Platelets
Have calcium in them (most clotting rxns need Ca2+)
Use purple top tube with K/EDTA
Purple top tube
Has K/EDTA EDTA => chelates Ca2+ and inhibits clotting
Calcium in clotting
Positively charged
Mediates binding of coagulation factor enzyme complexes via their negatively charged residues to negatively charged phospholipid surfaces of platelets
Ca is a bridge of positivity, allows platelets to act as scaffolds for clotting reactions
Alpha granules in platelets
Adhesion proteins (like Von Willebrands factor)
Common breed for Von Willebrand’s factor deficiency
Dobermans
Cat Platelets
Larger with a higher mean platelet volume (MPV) Especially sensitive to activation during blood sample collection
Snakes
Have thrombocytes Their platelets are very large and are an actual cell type
How to do a platelet estimate
- Count number of platelets in 10-100X oil immersion fields and average. 2. For dogs average count in 10 fields x 15,000/microLiter 3. For cats average count in 10 fields x 20,000/microLiter
Hemostasis
The arrest of bleeding.
Requires integrated response from blood vessels:
- endothelial cells
- collagen
- smooth muscle cells
- fibroblasts…..
and platelets, circulating clotting factors, and fibrinogen becoming fibrin.
Primary Hemostasis
Peripheral vasoconstriction occurs
Blood starts flowing again after momentary stoppage
Platelets start degranulating and releasing Ca2+ to form a platelet plug
(Endothelial defect exposes subendothelial collagen)
End result = platelet plug
Secondary Hemostasis
Stimulation of the coagulation system
Thrombin (Factor 2a) converts fibrinogen (Factor 1) to the active fibrin (Factor 1a)
Fibrin is incorporated into the clot and clot is stabilized
Coagulopathy
Excessive bleeding due to abnormal function/lack of presence of a coagulation factor.
Defect in secondary hemostasis usually leading to more severe bleeding than a platelet or primary hemostasis problem.
Coagulopathies lead to
Hemoabdomens, hemothoraxes, hemarthrosis, hematuria, and of course petechiae and purpura.
If there is a clot in the blood tube….
Don’t trust values from a hematology analyzer.
Automated platelet counts in cats….
Are NOT reliable.
Platelet counts
Lower in King Charles Spaniels and greyhounds.
King Charles Spaniels have a high prevalnce of
inherited asymptomatic thrombocytopenia with macrocytic platelets:
60-80,000 platelets can be normal
MPV
Large platelets are often young platelets
Platelet clumps will falsely decrease a plately count and falsely increase the MPV
Increased MPV
Seen in enhanced thrombopoiesis in response to thrombocytopenia
Thrombocytopenia often leads to
Petechiae, purpura, or ecchymoses.
-usually when less than 50,000/microLiter or less than that
Facial petechiae around the eyes
May be caused by a tight leash or a rabies pole.
Do a blood smear to look for platelets.
In a thrombocytopenic animal…
Do not use the jugular vein for blood, too close to the heart.
Do not poke organs, they may not stop bleeding.
Hall mark of tick-borne disease
Thrombocytopenia
Evan’s syndrome
Immune mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP) simultaneously.
Thrombocytopenia differentials
1. Decreased platelet production.
2. Increased platelet consumption.
3. Increased platelet destruction (most common cause)
Decreased platelet production
To assess do a bone marrow aspirate to look for sufficient platelet precursors, megakaryocytes.
Not enough megakaryocytes
Myelopthisis: space occupying lesion of bone marrow
Myeloproliferative diseases: Aplastic anemia, bone marrow not making anything ie: estrogen knocks out bone marrow in ferrets and dogs
Increased platelet consumption
DIC and thrombosis, vasculitis, hemangiosarcoma in dogs.
These animals will likely show changes in PT/PTT since platelets used up for clotting.
Increased platelet destruction
Most common cause of thrombocytopenia
Primary immune thrombocytopenia (ITP)
Secondary immune-mediated thrombocytopenias (drugs, infectious agents, neoplasia, SLE)
Vitamin K dependant clotting factors
2, 7, 9, 10
Vitamin K works by
inhibiting the enzyme, vitamin K epoxide reductase in the liver
-makes these factors hypofunctional
Which clotting test is prolonged first?
PT expected to be prolonged before PTT due to the short half-life of Factor 7.
Prolongation of PTT first is possible as well, depending on the species involved.
For the test think PT!!!!
Anticoaculation proteins
Anti-thrombin
Alpha 2 macroglobulin
Anti-thrombin
Stops thrombin from acting.
Thrombin converts fibrinogen to fibrin
Heparin keeps thrombin and anti-thrombin together
PLE
Protein losing enteropathy:
Low albumin and low globulin
PLN
Protein losing nephropathy.
Low albumin only.
Low antithrombin
Hypercoagulable state
DIC
PLN
PLE
Phase of clotting
- Vascular phase:
Exposure of subendothelial matrix and exposure of tissue factor (TF)
- Platelet phase:
Adhesion, activation, shape change, secretion (degranulation), aggregation
=> Platelet adhesion: Von Willebrands factor is how platelets adhere to each other and the vasculature (deficiency in dobermans)
Desmopressin
Stimulates transient release of von Willebrand factor from the endothelial cells.
von Willebrand factor
synthesized and released from endothelial cells and platelets
Major platelet agonists
PAF (Platelet activating factor)-made by cells of immune system, this is one way that inflammation and coagulatio are linked.
Intrinsic clotting cascade
12, 11, 9, 8 (PTT test) + common pathway
Extrinic clotting cascade
VII and TF (PT test) + common pathway
Common pathway
10, 5, 2, 1
How do you evaluate platelet function?
BMBT (buccal mucosal bleeding test)
Which clotting factor has the shortest half life?
Factor VIIa
Which clotting factor test would be prolonged if an animal got into a vitamin K rodenticide?
The animal will have a prolonged PT.
VIIa is an extrinsic pathway factor so use PT.
2, 7, 8, 10 all need vitamin K
Prolonged PT and PTT
Common clotting pathway is the problem