Lecture 8 - HAEM 5 Flashcards
Where is thrombopoietin (TPO) made?
Produced by various cells in the body - mainly by renal tubular epithelial, bone marrow stromal cells, hepatocytes
How does IL-6 stimulate thrombopoiesis?
IL-6 increases production of TPO by the liver –> thrombocytosis
Briefly explain how TPO can regulate thrombopoiesis?
TPO receptors on blood platelets and maturing magakaryocytes can bind internalise and degrade TPO providing negative feedback on platelet production
Briefly describe the kinetics of platelets:
Approximately 30% of circulating mass is transiently compartmentalised in spleen. Platelets circulate for approximately 5-9 days in most mammalian species
What are the two main reasons that there is frequently errors in feline blood platelet counts?
In standard collecting tubes - containing EDTA as an anticoagulant there is frequent (up to 71%) platelet aggregation
Another common error with feline platelet counts (PLT) is that many feline platelets are too big are not counted as platelets
Briefly explain how platelet counts work:
Volume detection is measured by changes in conductance.
The number of impulses = concentration of particles
Amplitude of impulsion = size of particles = types of cell
How many platelets should be seen per hpf (x100) under normal physiological conditions?
Dogs, cat, cattle = 8-10 plt/hpf
Horses = 5 plt/hpf
What is thrombocytopenia and what are the common clinical signs that accompany it?
A decrease in circulating platelets (most common acquired haemostatic disorder)
Clinical signs: petechiation or ecchymosis in tissues or mucosal membranes
What are the main causes of thrombocytopenia?
Decreased or defective platelet production - acquired megakaryocytic hypoplasia or aplasia
Increased platelet loss - massive trauma and extensive external haemorrhage
Accelerated consumption of platelets - DIC
Increased platelet destruction - primary (idiopathic), secondary - infectious agents, neoplasia, drugs, immune mediated
Abnormal platelet distribution
How frequent is selective megakaryocyte hypoplasia?
Rare - usually associated with defects of other lineages (Bi or pan-cytopenia)
What blood results would be seen with increased platelet loss as a result of increased platelet loss due to massive trauma or extensive external haemorrhage?
usually mild to moderate, transient and reversible thrombocytopenia
What blood results would be seen as a result of accelerated consumption of platelets and thrombotic microangiopathies?
Thrombocytopenia, haemolytic anaemia, and thrombosis
In what circumstances do patients with primary (idiopathic) IMT normally present and how is it diagnosed?
Haemorrhage involving skin and mucosal surfaced - may arise spontaneously or due to pathologic prolonged bleeding following oestrus, whelping, surgery, dentistry, grooming on venipuncture
In normal healthy animals what proportion of the platelet mass is stored in the spleen?
30% of platelet mass
What occurs in redistribution thrombocytopenia?
Where platelets become reversibly sequestered in tissues.
Mild to moderate thrombocytopenia may result from sequestration in animals with any condition associated with splenomegaly or hepatomegaly
What are the four main reasons that thrombocytosis may result?
- Physiologic - splenic contraction and epinephrine
- Drug induced - epinephrine and vincristine
- Reactive - inflammation, infection, neoplasia, trauma, rebound from thrombocytopenia
- Essential thrombocytopenia
Briefly explain how physiologic thrombocytosis may occur:
Up to one-third of platelets is normally sequestered in splenic red pulp - these stores can be released upon splenic contraction (a process that is mediated by epinephrine)
Briefly explain how vincristine and epinephrine induce thrombocytosis?
Vincristine - enhanced megakaryopoiesis
Epinephrine - induces a rapid, transient , thrombocytosis in dogs through splenic contraction
Briefly explain the cause of reactive thrombocytosis and the provide examples of conditions that could cause it:
Due to cytokine stimulation (mainly IL-6) of thrombopoiesis. Occurs secondarily to inflammation, infection, neoplasia, trauma, rebound from thrombocytopenia, iron deficiency related
What is the function of Von-Willebrand factor?
vWF = bridge between platelets and sub-endothelial matrix - binds platelets and collagen
What are the three different types of vWD?
Type 1 = equal decrease in all sizes of multimeters = quantitate change
Type 2 = decrease in only the large multimeters = qualitative change
Type 3 = no detectable vWF factor
What is Glanzmann thromboasthenia and what are the three main types of it?
Type 1: less than 5% of the receptor is detectable on platelet surface = clot retraction is invisible Type 2: 10-20%. of the receptor is present on platelet surfaces = clot retraction is detectable but reduced Variant: receptor is present but dysfunctional = clot retraction may or may not be detectable
