Term
| Why do cats display greater variability in platelet size than other mammals? |
|
Definition
altered M-loop region in beta1-tubulin
**this results in the presence of larger platelets and higher MPV in health in cats compared to other species |
|
|
Term
| What is the mean platelet circulating life span in dogs, cats, horses, and cattle? |
|
Definition
4-6 days
**longer in splenectomized dogs |
|
|
Term
| How does platelet glucose metabolism differ form that of RBC? |
|
Definition
Platelets have mitochondria so they use mainly oxidative phosphorylation to generate ATP (vs. RBC that use anaerobic glycolysis)
**platelets do also use glycolysis as well, esp. when platelets are activated and have high ATP demands |
|
|
Term
| Platelets of which species do NOT have a well developed canalicular system? |
|
Definition
|
|
Term
| What is a major component of platelet dense granules (asks delta-granules or dense bodies)? |
|
Definition
adenine nucleotides
also serotonin, Ca and inorganic polyphosphates
**these substances are secreted outside the platelet (degranulation) when activated |
|
|
Term
| What are the contents of platelet alpha granules? |
|
Definition
varies by species but in general alpha granules contain:
adhesive proteins (vWF, fibrinogen, fibronectin, thrombospondin)
coagulation factors (5, 7, 11, 23)
protease inhibitors (alpha2-antiplasmin)
chemokines (platelet factor 4, beta-thromboglobulin)
P selectin (CD62P)
GPIb (CD42)
GPIIb/IIIa (CD41/61) |
|
|
Term
| What glycoprotein is important for adhesion of platelets to vWF? |
|
Definition
|
|
Term
| What glycoprotein is important for platelet aggregation (e.g. binding to fibrinogen)? |
|
Definition
GPIIb/IIIa (CD41/61)
*deficiency in GPIIb/IIIa = Glanzmann's Thrombasthenia (great pyrenesse, otterhound/ unrelated mutation but similar phenotype in basset hounds and Finnish spitz) |
|
|
Term
| How does the platelet membrane change when activated and what is the effect on hemostasis? |
|
Definition
| When platelets are activated --> translocation of negatively charged phospholipids (mainly phosphaditylserine) from inner to outer leaflet. This provides a substrate for coagulation factors. |
|
|
Term
| How does the composition of the platelet membrane change when activated and what is the effect on hemostasis? |
|
Definition
| When platelets are activated --> translocation of negatively charged phospholipids (mainly phosphaditylserine) from inner to outer leaflet. This provides a substrate for coagulation factors. |
|
|
Term
| What is the effect of PF4 (CXCL4) [secreted by activated PLT from alpha granules]? |
|
Definition
| PF4(CXCL4) binds to heparin-like molecules on adjacent endothelial cells displacing antithrombin (which normally augments the anticoagulant activity of heparin) --> promoting coagulation |
|
|
Term
| What platelet product is thought to be involved in maintaining normal vascular integrity? |
|
Definition
|
|
Term
| What cell adhesion protein, other than vWF, can also bind to platelets (GP1b) to cause adhesion to sites of vascular injury under high flow/shear? |
|
Definition
| thrombospondin-1 (which is also contained in PLT alpha granules) |
|
|
Term
| What is the importance of the calcium diacylglycerol guanine nucleotide exchange factor 1 (CalDAG-GEF1)? |
|
Definition
CalDAG-GEF 1 promotes:
PLT aggregation- activation of platelet GpIIb/IIIa (binds fibrinogen), and increased synthesis of thromboxane A2 (also increases expression of GPIIb/IIIa)
PLT degranulation (via increased intracellular Ca+2)
***inherited defects in CalDAG-GEF1 have been reported in dogs and cattle and are associaited with defective PLT function and clinical bleeding |
|
|
Term
| What two intracellular signaling pathways are most important for platelet activation (secretion, shape change) and aggregation? |
|
Definition
Release of calcium from dense tubular system (via inositol triphosphate mediated binding to calcium channel receptor)
Protein kinase C activation (via 1,2-diacylglycerol aka DAG AND Ca ions) |
|
|
Term
| What are the major substances are involved in platelet activation (amongst other things)? |
|
Definition
| thromboxane A2, platelet activating factor, epinephrin (potentiates platelet activation by other agonists) |
|
|
Term
| What are some inhibitors to platelet activation produced by endothelial cells? What effect do these substances have on the vasculature? |
|
Definition
Prostacyclin/PGI2 (increase PLT cAMP) and nitric oxide (increase PLT cGMP) - both are potent vasodilators
Ecto-ADPase |
|
|
Term
| What PLT integrin functions in both platelet adhesion and as an agonist receptor that activates PLT? |
|
Definition
| alpha2beta1 integrin (collagen receptor) |
|
|
Term
| How are platelet granules secreted (dogs and cats, and most everything else)? |
|
Definition
| via open canalicular system which is continuous with the platelet surface- requires energy dependent actions of the surrounding microtubules and microfilaments that crush the granules together (fusion and dissolution) |
|
|
Term
| How does platelet granule secretion differ in ruminants, horses, and elephants, from other species? |
|
Definition
these species have a minimal open canalicular system so PLT granules and dense bodies release their contents by fusing with the outer PLT membrane
** as opposed to other species in which granules are crushed by microtubules and contents released into the open canalicular system |
|
|
Term
| What two substances are necessary for optimal platelet aggregation? How to these substances promote PLT aggregation? |
|
Definition
fibrinogen and calcium are necessary for optimal PLT aggregation by increasing exposure and activation of GPIIb/IIIa which binds to fibrinogen
*many other substances also contribute to PLT aggregation (e.g. ADP, thromboxane A2, thrombin, platelet activating factor, serotonin) |
|
|
Term
| What is the effect on coagulation of platelet microparticles? |
|
Definition
PLT microparticles have a procoagulant effect (they contain negatively charged phospholipid- phosphatidyl serine, adhesion molecules and possibility tissue factor)
**PLT microparticles are shed from activated platelets |
|
|
Term
| What is the only coagulation factor not normally present in circulation? |
|
Definition
| Tissue factor (Factor III) |
|
|
Term
| How does vitamin K activate the vitamin K dependent coagulation factors (factor 2, 7, 9, 10)? |
|
Definition
| Vitamin K dependent carboxylation (via gamma-glutamyl carboxylase) of glutamic acid residues on these molecules is necessary for them to bind Ca and become functional |
|
|
Term
| What species have gamma-glutamyl carboxylase deficiencies and what is the clinical manifestation of such? |
|
Definition
Cats and sheep --> results in bleeding episodes due to decreased activity of vitamin K dependent coagulation factors (2,7,9,10)
*gamma-glutamyl carboxylase is the vitamin K dependent enzyme in the liver that carboxylates glutamic acid residues on these coagulation factors, which allows them to bind Ca |
|
|
Term
| How do dicumarol-type anticoagulants (e.g. warfarin, brodifacoum) inhibit coagulation? |
|
Definition
dicumarol anticoagulants inhibit vitamin K epoxide reductase (VKOR)
*VKOR is needed to activate vitamin K for use in Vit K dependent carboxylase (to activate coagulation factors 2, 7, 9, 10) |
|
|
Term
| What is the main effect of tissue factor + Factor 7 mediated activation of coagulation? |
|
Definition
Amplification
TF+factor 7 result in generation of a small amount of fibrin (factor 1a) but more importantly also generated thrombin (factor 2a), which serves to amplify the procoagulant state via:
activating and aggregating PLT (provide large surface of negatively charged phospholipid and some species have coagulation factors in their granules (factor 5, 11).
cleavage of vWF/Factor 8, factor 8 stays on PLT surface
activation of factor 5 (free in circulation and from PLT granules) |
|
|
Term
| What coagulation factor is activated when activated factor 7 (a small amount is always in circulation) binds to tissue factor (e.g. perivascular cells)? |
|
Definition
factor 9
**factor 9 ultimately contributes to propagation of coagulation and formation of a burst of thrombin and fibrin via activated factor 10/5 complex |
|
|
Term
| Which of the coagulation factors does not play a major role in maintaining normal hemostasis in vivo? |
|
Definition
Factor 12
*animals with factor 12 deficiencies (or species that lack factor 12 such as birds, reptiles, and marine mammals) do not display any bleeding tendencies. |
|
|
Term
| What process is the propagation of coagulation? |
|
Definition
activation of the intrinsic pathway
*in vivo factor 12 probably plays a minor role (as no hemostatic defect is observed in deficient animals), so the intrinsic pathway really starts with factor 11 |
|
|
Term
| What coagulation factors are activated by thrombin? |
|
Definition
Factor 1 (fibrinogen is converted to fibrin by thrombin)
Factor 5 (factor 5 forms a complex with factor 10 that results in a burst of thrombin production to further amplify and propagate coagulation)
Factor 8
Factor 7 |
|
|
Term
| How does factor 12 activation and prekallikrein+high molecular weight kininogen contribute to both procoagulant and anti-coagulant effects? |
|
Definition
procoagulant: Activated factor 12 activates factor 11 and the intrinsic coagulation pathway
anticoagulant: activated factor 12 interacts with prekallikrein (bound to high molecular wight kininogen- HMK) which serves to generate more active factor 12 (procoagulant) AND kallikrein. Kallikrein interacts with HMK to generate bradykinin which stimulates release of tissue plasminogen activator from endothelial cells, promoting fibrinolysis. |
|
|
Term
| Why is activated factor 9 (generated by TF) better able to promote coagulation on adjacent platelet surfaces than factor 10 (also generated by TF)? *and hence only little fibrin is generated via TF pathway of coagulation alone* |
|
Definition
activated factor 10 quickly dissociated from TF bearing cells and is rapidly inactivated in the plasma (antithrombin and tissue factor pathway inhibitor) while factor 9 is much more resistant to inactivation
**factor 10/5 complex (prothrombinase) is not susceptible to inactivation and generates a large burst of thrombin --> fibrin |
|
|
Term
| What coagulation factor is responsible for catalyzing the formation of covalent cross links between fibrin monomers? |
|
Definition
|
|
Term
| What is the action of antithrombin? |
|
Definition
| antithrombin is the major thrombin inhibitor. It also inhibits other activated coagulation factors (9, 10, 11, 12) |
|
|
Term
| How do endothelial cells promote the action of antithrombin? |
|
Definition
Endothelial cells synthesize heparin sulfate proteoglycans which bind to antithrombin inducing a conformational change that enhances its affinity for thrombin*
**AT doesn't inhibit thrombin bound to platelets or fibrin so that localized, controlled coagulation can proceed where needed |
|
|
Term
| How does thrombomodulin (on endothelial cells) inhibit coagulation? |
|
Definition
| When thrombin is bound to thrombomodulin it can't activate other coagulation factors (factor 5, 8, 7) AND it activates protein C (which activates protein S --> inhibits factor 10 and TF-factor 7 complexes) |
|
|
Term
| How does activated protein C contribute to fibrinolysis, in addition to it's anticoagulant effects (Protein C activates protein S --> degradation of factors 5 and 8 on platelet surfaces AND --> activation of tissue factor pathway inhibitor --> inhibition of factor 10 and TF-factor 7 complexes)? |
|
Definition
| Activated protein C inactivates plasminogen activator inhibitor-1, which promotes fibrinolysis |
|
|
Term
| Describe the action of tissue factor pathway inhibitor? |
|
Definition
Anticoagulant
Tissue factor pathway inhibitor is activated by protein S and degrades TF-factor 7 complexes and activated factor 10 |
|
|
Term
| What anticoagulant substances can be secreted from platelet alpha granules? |
|
Definition
protease nexin-1 (inhibits thrombin)
proteas nexin-2 (inhibits factor 11)
Tissue factor pathway inhibitor (degrades TF-factor 7 complexes and Factor 10, when activated by protein S) |
|
|
Term
| What is the major activator of fibrinolysis? |
|
Definition
release of tissue plasminogen activator from damaged endothelium
*this may be augmented through the actions of Protein C (which inactivates plasminogen activator inhibitor-1) |
|
|
Term
| Does fibrinolysis occur more readily in capillaries or large vessels? |
|
Definition
| Fibrinolysis occurs more readily in capillaries. A higher density of endothelial cells in capillary beds results in more thrombomodulin-thrombin activation of protein C (inhibition of plasminogen activator inhibitor) and thrombin clearance, and greater release of tissue plasminogen activator. |
|
|
Term
| In addition to inactivation of thrombin, which other coagulation factors are are inhibited by antithrombin-heparin complexes? |
|
Definition
| factor 9, 10, and TF-factor 7 complexes |
|
|
Term
| What dog breeds typically have lower PLT counts than other breeds? |
|
Definition
| Greyhounds, cavalier king charles spaniels, Polish Ogar dogs |
|
|
Term
| How does MPV change in dogs with hypothyroidism vs. cats with hyperthyroidism? |
|
Definition
| MPV has been reported to be slightly higher in cats with hyperthyroidism and slightly lower in dogs with hypothyroidism compared to euthyroid animals |
|
|
Term
| What inherited RBC enzyme deficiency has been associated with mildly increased MPV and normal PLT in dogs? |
|
Definition
| phosphofructokinase deficiency |
|
|
Term
| APTT is prolonged in health individuals of what dog breed compared with other breeds? Why? |
|
Definition
Healthy Bernese mountain dogs have longer APTT compared with other dog breeds due to the presence of antiphospholipid antibodies (aka lupus anticoagulant)
**actually is associated with hyper-coagulability in vivo, these antibodies appear to prime platelets and endothelial cells for activation but a triggering event (e.g. infection, trauma, surgery) may be required for thrombosis to occur. |
|
|
Term
| Given that reference intervals for PT/PTT can very so much based on analyzer, what is one way to assess these tests without using RI? |
|
Definition
| Run a healthy species matched control at the same time. If the patient's sample is 30% longer than the control it represents an abnormal result |
|
|
Term
| What disorders are assessed by the thrombin clotting time? |
|
Definition
quantitative or qualitative fibrinogen disorders.
The test uses citrated plasma in which excess thrombin is added |
|
|
Term
| What diseases are associated with increased fibrinogen in dogs? |
|
Definition
| hyperadrenocorticism, pregnancy, nephrotic syndrome |
|
|
Term
| In what species have inherited fibrinogen deficiencies been reported? |
|
Definition
| dogs, cats, goats, and a lamb |
|
|
Term
| Why is the D-dmer assay specific to fibrinolysis (vs. FDP assays cannot distinguish between fibrinolysis and fibrinogenolysis)? |
|
Definition
| the D-dimer epitope is produced by factor 13 mediated cross linking of fibrin, so D-dimers are specific to fibrinolysis |
|
|
Term
| Which species has higher D-dimer concentrations in health? |
|
Definition
horses (up to 4x URI for d-dimers in people and dogs)
*D-dimer test is more sensitive for DIC in horses than FDP, but still not great (only about 50%) |
|
|
Term
| How does HCT affect TEG results? |
|
Definition
| high HCT corresponds to a more hypocoagulable TEG tracing, low HCT corresponds to a more hypercoagulable TEG tracing |
|
|
Term
| What conditions have been associated with increased vWF in dogs? |
|
Definition
Inflammation/inflammatory cytokines (IL-6, endotoxemia/sepsis)
exercise and epinephrine
pregnancy
IL-11 (stimulates megakaryocyte maturation amongst others
Vasopressin (stimulates release of vWF from endothelial Weibel-Palade bodies) |
|
|
Term
| In what species is antithrombin an acute phase protein? |
|
Definition
|
|
Term
| What is a more sensitive indicator of increased thrombopoisis than MPV? |
|
Definition
reticulated platelets (PLT <1 day old that contain increased amounts of RNA) - however, absolute reticulate PLT counts may not be increased in severe regenerative thrombocytopenia, possibly because reticulated PLT are consumed or destroyed at the same rate as mature PLT
**detected with thiazole orange fluorescent dye (can be done using sysmex PLT-O channel) |
|
|
Term
| What platelet surface markers can be used to detect platelet activation via flow cytometry? |
|
Definition
Annexin V (specific binding affinity for phospholipids (esp. PS) on activated PLT)
also presence of fibrinogen or P selection (CD62P) on PLT
presence of PLT-WBC aggregates and/or PLT microparticles have all been associated with platelet activation |
|
|
Term
| What platelet indice on automated flow cytometry based hematology analyzers (e.g. ADVIA) is associated with platelet activation? |
|
Definition
| decreased mean platelet component (MPC) is associated with platelet activation |
|
|
Term
| Platelet function analyzer (PFA-100) has limited utility in animals with what laboratory abnormality? |
|
Definition
| Anemia, closure time (e.g. clot formation time over the machine apperature) is significantly prolonged by decreased HCT so cannot be used to assess platelet function in anemic animals |
|
|
Term
| What two methodologies can be used to assess platelet aggregation? |
|
Definition
| Agonist (e.g. ADP, thrombin, collagen) are added to platelet-rich plasma and either assessed with a spectrophotometer (more aggregation = more light transmission) or electrical impedance (more aggregation = increased impedance between two electrodes) |
|
|
Term
| Why are anti-platelet antibody tests prone to false positives? |
|
Definition
| Platelets naturally have some immunoglobulin adsorbed to their surfaces and this can increased with time after blood collection resulting in false positive test results |
|
|
Term
| Other than increased platelet production in response to peripheral sequestration and/or consumption, what are some other diseases associated with macrothrombocytes? |
|
Definition
myeloid neoplasia
FeLV
inherited disorders (CKCS, May-Hegglin anomaly) |
|
|
Term
| In what species has neonatal alloimmune thrombocytopenia been reported? |
|
Definition
| horses, mules, pigs *rare, maternal antibodies against paternal PLT epitopes on the surface of neonatal platelets are transferred in colostrum |
|
|
Term
| What is the effect of GM-CSF and M-CSF on peripheral PLT? |
|
Definition
| decrease PLT due to activation of the monocyte macrophages system and premature clearance of platelets from circulation |
|
|
Term
| What does the term hypersplenism refer to? |
|
Definition
| splenomegally which results in increased removal of platelets and/or other blood cells by the spleen |
|
|
Term
| What cytokines inhibit bone marrow production of platelets? |
|
Definition
|
|
Term
| What infectious agents are associated with thrombocytopenia due to decreased platelet production? |
|
Definition
Typically viruses: parvo (dogs and cats)
FIV
FeLV |
|
|
Term
| What viruses have been associated with thrombocytopenia due to decreased marrow production AND increased platelet utilization/peripheral destruction? |
|
Definition
dogs: distemper horses: equine infectious anemia virus
Cows: bovine viral diarrhea virus
Pigs: classical swine fever virus (hog cholera), african swine fever virus |
|
|
Term
| What viruses have been associated with thrombocytopenia due to DIC? |
|
Definition
FIP
infectious canine hepatitis virus
african horse sickness virus |
|
|
Term
| How do tumors contribute to a procoagulant microenvironment that promote thrombosis, DIC, and platelet consumption? |
|
Definition
express tissue factor
release procoagulant micropartilces
secretion of cytokines that make endothelium procoagulant |
|
|
Term
| What gene is affected in cavalier kind charles spaniels with inherited macrothrombocytopenia? |
|
Definition
beta-1 tubulin
*may results in unstable alpha-beta tubular dimers within protofillaments resulting in abnormal proplatelet formation |
|
|
Term
| What is May Hegglin anomaly and in what breed of dogs has it been reported? |
|
Definition
[image]
has been reported in a pug, results from a mutation in MYH9, a gene that encodes for the heavy chain of nonmuscle myosin IIA. Hematologic abnormalities include:
leukocyte inclusions (prominent to pale blue, dhole-body to distemper like inclusions), thrombocytopenia, macrothrombocytes |
|
|
Term
| How do FDPs affect platelet function? |
|
Definition
| FDPs reduce platelet function by antagonizing fibrinogen binding to GPIIb/IIIa. |
|
|
Term
| What are some conditions associated with acquired platelet dysfunction? |
|
Definition
ITP (antiplatelet antibodies may interfere with GPIIb/IIIa (fibrinogen receptor) and GPIb/IX (vWF receptor)
FDPs (interfere with GPIIb/IIIa)
Paraproteinemia (multiple myeloma/lymphoid neoplasia, benign oligoclonal gammopathy)
Uremia
Liver disease (bile acids inhibit PLT function)
Drugs: NSAIDS (aspirin, bute)- inhibit thromboxane A2 synthesis [normally activates PLT], other drugs may interfere with PLT aggregation ( |
|
|
Term
| What deficiency is associated with glanzmann's thrombasthenia? |
|
Definition
Deficiency in the beta subunit of PLT GPIIb/IIIa, results in impaired PLT binding to fibrinogen and bleeding diathesis
dogs (great pyranese, otterhound)
horses (QH, peruvia paso, TB, Oldenburg) |
|
|
Term
| Mutations to which genre are associated with impaired GPIIb/IIIa function despite normal amounts of the protein? |
|
Definition
mutation to the gene encoding calcium diacylglycerol guanine nucleotide exchange factor 1 results in altered intraplatelet signaling --> impaired platelet activation and impaired GPIIb/IIIa function
**this has been reported in Basset hounds, Finish spitz, Landseer dogs and Simmental cattle |
|
|
Term
| What is the effect of a mutation in Kindlin-3? |
|
Definition
impaired activation of beta2 integrin in WBC and PLT --> impaired leukocyte extravasation and PLT aggregation --> increased susceptibility to infection and life threatening hemorrhage
*has been reported in german shepherd |
|
|
Term
| What are the clinical and clinicopathologic features of chediak-higashi syndrome? In what species has it been reported? |
|
Definition
[image]
Partial albanism, increased susceptibility to infection, bleeding tendencies and the presence of many enlarged (pink-purple) membrane bound granules in the cytoplasm of many cells (including WBC) that are thought to arise from impaired fusion of primary lysosomes during cell development . Bleeding tendencies are the result of platelet dense granule deficiency.
Affect animals: persian cats, cattle, aleutian mink, foxes, beige rats and a killer whale |
|
|
Term
| Mutations to which gene are associated with cyclic hematopoiesis in dogs? |
|
Definition
AP3B1
Dog with cyclic hematapoisis will have episodes of bone marrow megakaryoyte hypoplasia but typically not peripheral thrombocytopenia because periods of decreased platelet production are short relative to platelet circulating lifespan. |
|
|
Term
| What inherited platelet disorder is associated with clinical hemorrhages more suggestive of a secondary hemostatic disorder (e.g. intramuscular hemorrhage, hyphema)? |
|
Definition
Scott syndrome (reported in a family of german shepherds)- molecular defect(s) unknown
Diminished phosphatidyl serine on the surface of platelets results in diminished surface for coagulation factor reactions to proceed
**PLT function (phospholipid not necessary for platelet adhesion and aggregation) and in vitro coagulation tests were all normal (performed on citrated plasma without PLT). No TEG abnormalities either |
|
|
Term
| Which type of vWD is associated with most severe hemorrhage? |
|
Definition
Type 2 (disproportionate loss of high molecular weight VWF polymers) -german short haired and wire haired pointers, QH, TB, simmental cow
Type 3 (virtually no vWF in plasma, may also have decreased concentrations of factor 8- although not enough to prolong PTT)- Dutch kookier, Scottish terrier, Shetland sheepdog, pigs, himalayan cat |
|
|
Term
| What percentage of normal vWF activity is associated with clinical hemorrhage in affected dogs with Type I vWF? |
|
Definition
<20%
*type 1 vWF is associated with proportionally decreased concentrations of vWF multimers |
|
|
Term
| What findings with a platelet function analyzer (PFA-100) are associated with vWD in dogs? |
|
Definition
| prolonged ADP/collagen closure time |
|
|
Term
| T/F erythropoietin can induce thrombocytosis? |
|
Definition
True
thrombocytosis has been reported in cats and dogs following treatment with recombinant erythropoietin AND in association with neoplasms that may produce erythropoietin (e.g. hepatoblastoma, renal adenocarcinoma) |
|
|
Term
| What laboratory test provides the best evidence of a hypercoagulable state? |
|
Definition
Increased Thrombin-antithrombin (TAT) complexes
provides the best indirect evidence of increased thrombin generation in vivo |
|
|
Term
| How does inflammation contribute to a hypercoagulable state? |
|
Definition
IL-6 stimulates increased thrombopoitin production by the liver --> increased platelet mass
IL-6 and other inflammatory cytokines cause platelet hyperreactivity
Increased fibrinogen (positive acute phase protein) and hypofibrinolysis (plasminogen activator inhibitor is a positive acute phase protein) |
|
|
Term
| What disorders in small animals are most often associated with a hypercoagulable state via TEG? |
|
Definition
IMHA
Parvo enteritis (dogs)
malignant neoplasia (~50% are hypercoagulable) |
|
|
Term
| What contributes to the development of a hypercoagulable state in dogs with hyperadrenocorticism? |
|
Definition
Increased concentrations of coagulation factors (factors 1 (fibrinogen), 2 (prothrombin), 5, 7, 9, 10, 12)
decreased antithrombin |
|
|
Term
| What contributes to the development of a hypercoagulable state in horses with ischemic/inflammatory GI disease? |
|
Definition
Decreased antithrombin and protein C
**may not be hypercoagulable on TEG |
|
|
Term
| What disease in cats is associated with a hypercoagulable state in almost half of affected individuals? |
|
Definition
| hypertrophic cardiomyopathy |
|
|
Term
| What laboratory test is most sensitive for the diagnosis of localized thrombosis (i.e. thromboembolism)? |
|
Definition
D-dimmers (high sensitivity and high negative predictive value for diagnosis of thromboembolic disease) - in DOG and CATS, less sensitive (~50%) in horses (but still more sensitive than FDPs)
**rule out thromboembolism (and DIC) if D-dimers are not elevated |
|
|
Term
| What is the general initiator of DIC? |
|
Definition
DIC is generally initiated by the disseminated presentation of tissue factor in the blood
(e.g. widespread endothelial injury, pro-inflammatory cytokines that stimulate TF expression on monocytes +/- endothelial cells, circulating neoplastic cells) |
|
|
Term
| Hemorhage secondary to DIC is most common in which species? |
|
Definition
Dogs
*relatively uncommon in cats and horses |
|
|
Term
| What is the pathogenesis of hemolytic uremic syndrome? |
|
Definition
*Rarely reported in dogs (with gastroenteritis) and horses/cattle (with endometritis)*
Shiga toxin (produced by e. coli and shigella dysenteriae that colonize the intestine, usually not bacteremic) damages endothelial cells resulting in platelet activation and aggregation --> thrombocytopenia, microthrombi formation often causing AKI, hemolysis
Atypical hemolytic uremic syndrome (secondary to other diseases) has been reported in a small cohort of cats treated with cyclosporine following renal transplant |
|
|
Term
| What is the mechanism of coagulopathy associated with aflatoxin B1 toxicity? |
|
Definition
Decreased hepatic production of coagulation factors
*if there is severe hepatic necrosis DIC may also develop |
|
|
Term
| Why is snake envenomation from pit vipers associated with massively increased FDP and hypocoagulable state? |
|
Definition
the venom of these snakes has thrombin-like activity, but they only partially convert fibrinogen to fibrin and do not activate factor 13 (so no cross-linking) resulting in the formation of highly friable clots that are quickly degraded into FDPs following release of tissue plasminogen activator from endothelial cells.
FDPs have anticoagulant effects (FDPs reduce platelet function by antagonizing fibrinogen binding to GPIIb/IIIa) and the massive utilization of fibrinogen as a result of the venom results in hypofibrinogenemia and hypocoagulable state/bleeding. Thrombocytopenia may also develop from platelet activation and aggregation secondary to vascular injury or direct action of the venom itself. |
|
|
Term
| which inherited specific coagulation factor deficiency is associated with the most clinically severe hemmorhage? |
|
Definition
Factor 10 deficiency (cocker spaniels, Jack russel terrier, DSH)
Other factor deficiencies are either asymptomatic (factor 12, prekallikrein) or may be associated with mild hemorrhage following trauma or sx (factor 11, factor 7)
*Animals with Vit K dependent factor deficiencies (due to deficiency in gamma-glutamyl-carboxylase) exhibit variable bleeding tendencies but fatal hemorrhagic episodes are possible (esp. devon rex cats) |
|
|
Term
| What pre-analytical and physiologic factors can result in an artifactual prolonged PTT with a normal PT? |
|
Definition
| decreased plasma:anticoagulant ratio (e.g. underfilled citrate tubes) or hemoconcentration/erythrocytosis) |
|
|
