seraclues's version from 2015-09-07 07:53

Platelet formation and primary haemostasis

Question Answer
what 2 mediators are released by normal endothelial cells, in order to prevent clotting?NO and PGI2
List the 4 steps of haemostasisvasoconstriction and platelet plug (1); Coagulation-->fibrin(2); fibrinolysis; repair
Define thrombopoiesisplatelet formation
What is the parent cell in thrombopoeisis, and what tells it to develop?Megakaryocytes, under the influence of thrombopoetin
How long does megakaryocyte maturation take?2-10 days, depending on the species
describe the look of Megakaryocyte8-32 nuclei, with a huge cytoplasm and red/purple granules
Describet he look of a plateletsmall packets of granules with a pale bue cytoplasm
List the four ways platelet numbers are affectedproduction in BM or spleen; consumption; redistribution into or out of spleen; destruction by macros in the spleen or liver
Why woudl a platelet by normally destroyed in the spleen/liver?if carrying ABs or compliment
Explain what happens during primary haemostasisvasoconstriction due to neurogenic reflex and mediators, platelets adhere to subendothelial collagen (Von Will. factor may help to bridge), platelets release granules which tell others to change shape and agregate, platelets contract together to form plug
what compound is released by a newly shaped platelet, to tell others to aggregate?ThromboxaneA2

PRIMARY HAEM. DISORDERS: defects in numbers and function of platelets

Question Answer
What 5 conditions may result in thrombocytosis?splenectomy, neoplasia, inflammation, haemolytic disease, and iron deficiency
What 3 dog breeds may give falsely low thrombocytopenia?KingCharles (has microplatelets that may not be coutned), Greyhounds and Shiba Inus (have naturally lower counts)
At what level of platelets does spontaneous bleeding occur?<25x10(9) cells/L, or higher if there's a demand eg surgery or trauma
List four reasons thrombocytopenia may be due to decreased production?Bone Marrow Pnahypolasia/bovine neonatal pancytopenia, pure megakaryocytic hypolasia, myelophthisis, or infectious agents
Explain the clinical presetation of Bone marrow PanyhypoplasiaDue to damaged stem cells. You see neutropenia first, then thrombocytopenia, then non-regenerative anaemia
What is the cause of Pure Megakaryocytic hypoplasia?immune-mediated, against megakaryocytes
What is myelophthisis?Neoplasia or fibrous tissue occupying the space of the bone marrow
What is the most common cause for increased consumption, resulting in cytopenia?DIC- vasculitis and edocarditis causes altered eno cells, or exposed subendothelial collagen
Why disease woudl cause icnreased sequestration, resulting in thrombocytopenia?spelnic neoplasia, causing congestion or enlargements
What is the most common cause of increased destruction of platelets in dogs, leading to thrombocytopenia?Idiopathic Immune-mediated thrombocytopenia
what are 5 causes of thrombocytopathy (normal numbers, but abnormal function?)Drugs, uraemia, DIC, Liver disease, and hyperglobulinaemia (plasma cell myeloma)
List 2 drugs that can cause thrombocytopathy, and how so?COX inhibitors inhibit coxegenase for 6 hours. Usually okay, but if another underlying problem (VWD or thromb'penia) then can bleed. B-lactam ABs and calcium-channel blockers (barbiturates) can impain platelet activation.
How does DIC impair platelet function?There are increased numbers of Fibrin Degradation Products (FDP) that bind and swith off the platelets
How does Liver disease impain platelet fucntion?If diseased, it may not be clearing the FDP properly, so they bind and turn plaetels off

PRIMARY HAEM. DISORDERS: Von willebran's Disease (VWD), DIC and vessel wall defects

Question Answer
Where is VW factor produced from?Megakaryotyctes and endothelial cells
What are the 2 functions of VW factor?To glue platelets to exposed subendothelial collagen, and to increase adhesion of platelets to each other
In what species in VWD common? (rare in others)dogs
There are 3 types of VWD. which one are we concerned with?Type 1 VWD
define Type 1 VWDdeficiency of VW factor, by at least 50%. It is autosomal dominant inheritance.
Which breed is most common to be affected by VWD?Dobermans mostly
Define DICPathological activation of the clotting system, leading to generalise intravascular clotting, mainly in arterioles and capillaries
DIC may result in what 3 changes?widespread tissue/capillary damage; release of tissue factor from cells; production of large numbers of procoagulant proteins
Is DIC hyper or hypo coagulable?It could be either, depending of the balance of what it causes. ie is there more tissue factor released, or more procoagulant proteins released?
What are the 6 clinical signs of DIC?haemorrhage or thromboembolisms, increased PT and APTT, Decreased fibrinogen, Schistocytes on blood smears, increased FDPs, and decreased antithrombin3 activity
We cannot test for FDPs in NZ. What do we test instead?D-dimers, which are an FDP at the end of fibrin breakdown. Absence of them doesnt' rule out DIC though.
Give two infectious causes of vasculitis, causing bleeding?Infectious Canine Hepatitis and MCF
In hat species does VitC deficient diets result in vasulitis and bleeding?Guinea pigs and primates
What is the clinical presentation of scurvey?Petichea and ecchymosis mainly around the joints.

Laboratory evaluation of PRIMARY HAEM.

Question Answer
list the 3 tests done to evaluate primary haemostasisPlatelet count (always first step); BMBT; vWF antigen assay
Describe the process of doing a platelet countDone on anticoagulated whole blood, ideally EDTA tube. Manual if necessary. Check feathered edge to check for clumping
Describe the process of doing a BMBTused if platelet count is normal, but you're still suspicious. Surgicutt tool, incision into the buccal mucosa and count time till it stops.
Describe the process of doing a VWF antigen assaySodium citrate tube. Immediately spin to separate the plasma, and freeze it. send to lab with 2 weeks.
What are the normal platelet count numbers for cats and dogs?dogs 12-15 per HPF, cats 10-12 per HPF. <3 will cause spontaneous bleeding
What is the normal BMBT for a dog?<4 minutes. Average of 2.5minutesf is normal.
What does a long BMBT indicate?thrombocytopenia, vWD, thrombocytopathy (function), or vessel wall defect


Question Answer
list the clotting cascade in the intrinsic pathwayTriggered by contact activation, when HMWK, PK and Factor 7 contact a negatively charged surface. Then F11->9->8. Factor 8 can activate FX and the common pathway
List the clotting cascade in the extrinsic pathwayInitiated by Tissue Factor 3 (thromboplastin) interacting with Factor 7. Factor 7 can activate FX and the common pathway.
List the cascade of the common pathwayEither F8 (Intrinsic) or F7 (extrinsic) can activate it. Turns prothrombin to thrombin, which turns fibrinogen8 into a fibrin clot.
Where are most coagulation and fibrinolytic factors and many coagulation inhibitors producedIn the liver. hence liver function is vital for haemostasis.
What role does Calcium play in haemostasisIs it essential as it acts as a bridge between factors. That's why it's in EDTA, Ca Citrate and oxalate tubes for blood collection.
What role does vitamin K play in haemostasis?It is required to activate clotting factors 2, 6, 9 and 10.
What initiates fibrinolysis?Activcated plasminogen in the blood dissolves fibrinogen and fibrin into FDPs (eg D-dimers).

Disorders of SECONDARY HAEM.

Question Answer
Haemophilia A is an inctrinsic defect. What is it caused by?deficiency in Factor 8.
How does Haemophilia A affect different species?Dogs; variable severity in bleeding. Horses; severe bleeding. Cats; mild bleeding
How is Haemophila A aquired?It is X-linked inherited. So the males bleed spontaneously (have <10% of normal F8 levels) and females are carriers but don't bleed (40-60% of F8 levels)
Name three intrinsic pathway defects, and state the most common.Haemophilia A, B, and Factor 11 deficiency
Haemophilia B is an intrinsic pathway defect. What is it caused by?Deificeincy in Factor 9, in cats and dog. Again, it is X-linked.
Factor 11 deficiency is an intrinsic pathway deficiency. Which species are susceptible?only in dogs and Holstein cattle
Give an example of an extrinsic pathway defectBy themselves, extrinsic defects are rare. An example is rat bait toxicity.
List four defects of the combined extinsic and intrinsic pathwaysVitamin K deficiency (coumarin toxicity), DIC, severe liver disease, and just the dilutional effect of fluid administration

Defects of combine ext. and intr. pathways

Question Answer
Why is vitamin k necessary for haemostasis and what happens in a deficiency?needed for the activatin of some factors (2,7,9 and 10). Bleeding usually occurs 3-7 days after exposure to comourin toxicity
What will be the diagnostic test results of vitamin k deficiency (comourin toxicity)?increased APTT and PT. ut in the early stages, only increased PT, becuase F7 has the shortest half-life so runs out first.
What is the best test for monitoring vitamin k deficiency?PT, becuase it will show up first, when F7 runs out (short half-life)
What will be teh diagnostic test results of severe liver disease?increased APTT and PT


Question Answer
Prothrombin Time (PT)extrinsic or common pathways
Activated Partial Thromboplastin Time (APTT)Intrinsic or common pathway
Thrombin Time (TT)measure of fibrinogen
Activcated Coagulation Time (ACT)In-clinic vesrious of APTT. Intrinsic or common.
What is special about ACT tubes?They have a substance that promotes intrinsic activation (often diatomacous earth)
Normal ACT for a dog: 60-95 seconds
Normal ACT for a cat: 50-75 seconds
Question Answer
What temperature must an ACT test be done at?37 degrees