Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Lymphoreticular and haematopoeitic > Coagulopathies 1&2 > Flashcards

Coagulopathies 1&2 Flashcards

1
Q

Define haemostasis

A

The interaction b/w BVs, PLTs and coagulation factors that normally maintains blood in a fluid state and allows for formation of PLT plugs and clots when vessels are injured

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

4 components of haemostasis

A
  • endothelium
  • PLT
  • coagulation factors
  • fibrinolytic factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Result of abnormal haemostasis

A

haemorrhage or thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Outline endothelial cells in haemostasis

A
  • flattened cells that line BVs
  • have pro- and anticoagulant properties
  • normally are anticoagulant
  • act as barrier to subendothelial collagen which is procaogulant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe von Willebrand’s factor (vWF)

A
  • produced by endothelium and PLTs
  • stored in Weibel Palade bodies
  • released early in haemostatic process
  • responsible for PLT adhesion to collagen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe PLTs

A
  • small, discoid, anuclear cells found in circulation
  • 3-5 micrometers, pale basophilic, small red granules
  • derived from cytoplasm of megakaryocytes in BM (thrombopoiesis)
  • mediated by thrombopoietin
  • circulate for 5-9d (most spp)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe PLT structure

A
  • OM contains Rs for adhesion and aggregation
  • contain cytoskeleton with actin and myosin that allows for shape change
  • contain membrane bound granules (alpha granules are red and contain vWF, fibrinogen an factors 5 and 8.. Dense granules contain ADP and Ca)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe PLT surface receptors

A
  • Gps associated with PLT membrane
  • GP1b binds vWF
  • GP2b3a binds fibrinogen on adjacent PLTs and allows PLTs to aggregate
  • defects in Rs lead to abnormal PLT function and clot formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Stages of haemostasis

A
  • PRIMARY: formation of primary PLT plug
  • SECONDARY: activation of coagulation cascade and generation of insoluble fibrin which stabilises the PLT plug
  • FIBRINOLYSIS: breakdown of fibrin and PLT plug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Steps in primary haemostasis

A
  • damage to endothelium and exposure of subendothelial collagen
  • vWF released from damaged endothelium
  • PLT adhesion occurs
  • PLTs bind to collagen via R GP1b and vWF from endothelium
  • once PLTs have adhered to collagen, they undergo shape change and become spherical with filipodia
  • additional receptors for vWF (GP1b) and fibrinogen (GP2b3a) are exposed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe PLT aggregation

A
  • PLTs bind fibrinogen via GP2b3a
  • this occurs b/w adjacent PLTs thereby forming a clump/aggregate of PLTs
  • fibrinogen is generated from the coagulation cascade, it is released from PLTs and found in plasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe PLT secretion

A
  • aggregating PLTs rapidly degranulate
  • release of ADP, fibrinogen, vWF
  • Thromboxane A2 also released from PLT membrane
  • these all increase PLT adhesion and aggregation
  • PLTs also release factors 5 and 8 which are involved in coagulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe secondary haemostasis

A
  • involves activation of coagulation cascade
  • soluble enzymes (serine proteases) found in circulation
  • each step of coagulation cascade converts one of these factors from an inactive stage (proenzyme) to its active state
  • each step amplifies the system
  • end result is the formation of insoluble fibrin
  • fibrin stabilises the primary PLT plug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Outline the coagulation cascade

A
  • divided into intrinsic, extrinsic, common pathways
  • done to facilitate lab tests
  • division doesn’t exist in vivo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the extrinsic system (initiation)

A
  • most important in vivo
  • tissue factor (TF) released from damaged tissue binds to and activates F8 in presence of Ca
  • TF-F8 complex activates F5 of the common pathway and F9 of the intrinsic pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the intrinsic pathway (amplification)

A
  • F7 is activated by contact with a negatively charged surface (cofactor HMWK)
  • activated F8 cleaves and activates F11 which in turn activates F9 (calcium required)
  • activated F9 in turn activates F10 of the common pathway (calcium required)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the common pathway

A
  • starts with activation of factor 10
  • activated F10 binds activated F5 and calcium on PLT surface
  • this complex converts prothrombin (F2) to thrombin (F2a)
  • thrombin converts fibrinogen (F1) to fibrin (F1a)
  • fibrin crosslinked by activated F13
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are inhibitors of coagulation?

A
  • Antithrombin 3: inhibits thrombin and activated F10
  • Activity of AT3 increased by heparin from endothelium
  • Protein C: inactivates factors 5 and 8
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Outline fibrinolysis

A
  • enzymatic breakdown of fibrin by plasmin
  • plasmin is derived from plasminogen found in PLT membrane and plasma
  • plasmin degrade to both fibrinogen and fibrin to produce Fibrin Degradation Products (FDPs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe lab evaluation of PLTs by PLT concentration

A
  • automated counts can be done on PLTs collected into EDTA as part of CBC
  • good accuracy for all spp except cat/sheep/ goat d/t overlap b/w RBC and PLT size (i.e. small RBCs)
  • PLT clumps also cause inaccurate counts d/t lack of even distribution and d/t overlap in size b/w clumps and RBCs (v. common in cats)
  • can also estimate PLT count by SMEAR. Must be done in cats and CKCS as latter often thrombocytopaenic with giant PLTs which may be counted as RBCs d/t large size
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe interpretation of PLT numbers

A
  • upper reference limit (>1000*1069/L) are consistent with THROMBOCYTOSIS and may be associated with increased risk of thrombosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does buccal mucosal bleeding time assess?

A
  • PLTs function (not number)
  • measures length of time for PLT plug to form: evaluates primary haemostasis and PLT function
  • use spring loaded cassette to make small incision into buccal mucosa and blood is blotted until bleeding stops
  • v low sensitivity
  • INCREASED: if thrombocytopaenia, vWF dz, disorders of PLT function. Will NOT be increased with coagulation deficiencies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Name 3 disorders of PLTs

A
  • thrombcytopaenia
  • thrombocytosis
  • disorders of PLT function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What can PLT disorders lead to?

A
  • haemorrhage if PLT numbers are decreased or function is impaired. typically seen as ecchymoses or petechiae
  • can lead to increased risk of thrombosis if numbers increased
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Thrombocytopaenia mechanisms

A
  • INCREASED PLT DESTRUCTION OR CONSUMPTION: immune-mediated, haemorrhage, DIC, sequestration
  • DECREASED PRODUCTION (BM problem)
  • INFECTIOUS: numerous causes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Outline immune-mediated thrombocytopaenia (IMTP)

A
  • commonest cause of thrombocytopaenia

- PLT numbers often v low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is Evan’s syndrome?

A

concurrent immune-mediated thrombocytopaenia and anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How are RBCs normally destroyed?

A

Majority destroyed in periphery, subset can be destroyed by megakaryocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Types of IMTP

A
  • PRIMARY: Abs are produced against PLT antigens

- SECONDRAY: other immune dz (SLE), drugs/vaccine / injection, neoplasia, infectious

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

CS - IMTP

A
  • profound thrombocytopaenia (always recheck #s, look for clumps on smear and clots in tube)
  • evidence of petechial or ecchymotic haemorrhages
  • Hx of bleeding from gums, mucosal surfaces, prolonged bleeding from wounds etc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Dx - IMTP

A
  • difficult to confirm as dx of exclusion
  • may see megakaryocyte hyerplasia (BM)
  • BM exam can be done even if PLT #s v low - animals rarely bleed from this site
  • Anti-platelet Ab - need large volumes of blood as PLT #s will be low
  • response to tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Causes - thrombocytopaenia

A
  • INCREASED CONSUMPTION
  • SEQUESTRATION
  • DECREASED PRODUCTION
  • INFECTION
33
Q

Outline increased consumption as cause of thrombocytopaenia

A
  • haemorrhage: #s shouldn’t be lower than 100*10^9/L
  • DIC: #s may be v low
  • usually with DIC there will be other signs of a coagulation defect
  • check PT, PTT - prolonged
  • check FDPs - decreased
34
Q

Outline sequestration as a cause of thrombocytopaenia

A

Rare but may occur with splenomegaly or with large cavitated mass

35
Q

Outline decreased production as a cause of thrombocytopaenia

A
  • BM dz
  • neoplasia
  • drugs
36
Q

Outline infectious causes of thrombocytopaenia

A
  • number of causes possible including immune-mediated and decreased production: FeLV, BVD, Ehrlichia, Leishmania
37
Q

List some disorders of PLT function

A
  • Glanzmann’s thrombocytopaenia - defect in GP2b3a
  • Canine thrombopathia - abnormal GP2b3a exposure and impaired degranulation
  • Bovine thrombopathia - defect not known
38
Q

Describe Glanzmann’s thrombocytopaenia

A
  • defect in GP2b3a
  • otterhounds and Great Pyrenees
  • Quarter horse
  • defective PLT aggegation and abnormal clot retraction
39
Q

Describe canine thrombopathia

A
  • abnormal GP2b3a exposure and impaired degranulation

- Basset hounds

40
Q

Describe bovine thrombopathia

A
  • defect not known
  • simmentals
  • mild to severe bleeding
41
Q

3 broad causes of thrombocytosis

A
  • physiological (tx)
  • reactive (secondary)
  • essential thrombocythemia
42
Q

What can cause transient physiological thrombocytosis?

A

epinephrine induced splenic contraction

43
Q

Describe reactive (secondary) thrombocytosis

A
  • increased thrombopoeitin and possibly IL-6

- inflammation, haemorrhage, iron deficiency

44
Q

Outline essential thrombocythemia

A
  • PLT equivalent of leukaemia
  • myeloproliferative disorder
  • marked persistent increase in PLTs
  • BM megakaryocytes increased and may have abnormal morphology
  • function variable - may see petechiae and ecchymoses or thrombosis
  • TPO levels normal or increased
45
Q

Describe von Willebrand’s disease

A
  • vWF is a plasma GP needed for PLT adherence to collagen and formation of primary haemostatic plug
  • synthesised by endothelial cells, PLTs and megakaryocytes- circulates bound to F8 (protective function of F8)
  • may see concurrent decrease in F8
  • exists in small, medium and large multimers: large multimers are the most active in haemostasis
  • common in dogs, rare in cats/horses
  • 3 types
46
Q

CS - von Willebrand’s disease

A
  • mucosal bleeding (GIT, epistaxis, haematuria)
  • bleeding may be absent
  • no petechiae (differentiate it from other PLT disorders)
  • see prolonged buccal mucosal bleeding time w/o thrombocytopaenia
  • ## clotting times usually normal but PTT may be prolonged d/t decrease in F8
47
Q

Type 1 von Willebrand’s disease

A
  • ALL multimers present but at decreased concentrations

- variable severity of bleeding but not until concentration of vWF are

48
Q

Type 2 von Willebrand’s disease

A
  • qualitative abnormalities in vWF structure and function
  • often disproportionate decrease in large multimers
  • severe and uncommon
  • seen in german shorthaired and wirehaired pointers, one horse case
  • autosomal recessive
49
Q

Type 3 von Willebrand’s disease

A

absence of all vWF multimers

50
Q

Tests/Dx for von Willebrand’s disease

A
  • measure levels of vWF Ag
  • collect blood into EDTA or citrate (for latter, ensure blood: citrate ratio of 1:9)
  • vWF levels will be decreased by clots in the sample and by hemolysis but are unaffected by lipemia
  • separate plasma immediately, freeze and ship with ice
  • ELISA: quantitative measurement of vWF using species specific Abs,
51
Q

Interpretation of vWF ELISA

A

-

52
Q

Tx - vWD

A
  • transfusion to supply vWF
  • CRYOPRECIPITATE best as concentration of vWF 5-10 times greater than plasma, give 1 IU/10kg
  • PLASMA at 6-12ml/kg if cryoprecipitate not available
  • whole blood if animal is anemic
  • desmopressin (DDAVO) as preop prophylaxis for dogs with type 1, causes release of vWF from endothelium, give 1microg/kg SC 30 min prior to sx, also an IN preparation available
53
Q

Outline sample collection for lab evaluation of coagulation

A
  • citrated plasma (most tests)
  • ratio of anticoagulant: blood should be 1:9 (fill to line), always check for clots
  • don’t sample through herparinised catheters
  • minimise trauma when collecting blood otherwise will activate PLTs and coagulation
  • centrifuge to separate plasma within 1hr
  • analyse within 4 hrs or freeze plasma
  • always include a spp specific control
54
Q

Describe the ACT test

A
  • Activated Clotting Time
  • evaluates intrinsic and common pathways
  • collect 2ml whole blood into ACT tube containing diatomaceous earth
  • incubate for 60s at 37 degrees and check for clots every 5-10s
  • time to initial signs of clot is the ACT (s)
  • interpretation similar to PTT but less sensitive
  • will be prolonged with thrombocytopaenia
55
Q

Describe the PTT test

A

= Partial Thromboplastin Time

  • screening test for intrinsic and common pathways
  • incubate citrated plasma with excess phospholipid, contact activator and calcium
  • measure time to formation of clot
  • lipemia, hemolysis, oxyglobin tx and icterus interfere with clot formation
56
Q

Explain PTT interpretation

A
  • prolonged PTT indicates defect in intrinsic factors (12, 11, 9 and 8) or common pathways (F10, 5, 2 and fibrinogen)
  • factor activity must be
57
Q

Describe the PT test

A
  • prothrombin time
  • screening for defects in extrinsic and common pathways
  • incubate citrated plasma with tissue thromboplastin (TF) and calcium
  • measure time to clot formation
58
Q

Explain PT interpretation

A
  • prolonged PT indicates defect in extrinsic (factor 7) or common pathways of coagulation
  • Factor activity must be
59
Q

Which coagulation tests measure intrinsic and common pathways?

A

PTT and ACT

60
Q

Which coagulation test measures the extrinsic and common pathways?

A

PT

61
Q

What are other coagulation tests?

A
  • specific factor analysis
  • to detect specific factor deficiencies
  • usually done to detect hereditary deficiencies
  • done by correcting PT and PTT of test plasma with normal plasma
62
Q

What are tests of fibrinolysis?

A

= FDPs

  • use latex agglutination test
  • special test and kit requires specialised tubes so lab needs to be contacted
  • done on serum (needs to be separated within 30 minutes)
  • test immediately or freeze
  • INCREASED FDPs: with DIC
  • not specific
  • may also increase with haemorrhage, jugular vein thrombosis (horse) and liver disease
  • D-dimers: plasmin mediated degradation of cross-linked fibrin, detects fibrinolysis after fibrin cross-linking
63
Q

Examples - disorders of coagulation

A
  • acquired factor deficiencies
  • main one is the result of vit K deficiency
  • typically with rodenticide toxicity (coumarin, indanedione) or sweet clover ingestion (cattle)
  • vit K dependent factors are factors 2, 7, 9 and 10.
64
Q

Outline mechanism of vit K deficiency

A
  • factors 2, 7, 9 and 10 are produced in liver
  • are activated by vit K dependent carboxylase: this step requires reduced vit K
  • production of reduced vit K requires action of vit K reductase
  • vit K reductase inhibited by coumarin type rodenticides
  • leads to lack of active factors 2, 7, 9 and 10 and a coagulopathy
  • extrinsic, intrinsic and common pathways affected
  • factor 7 has shortest half life so will decrease first
  • PT is often prolonged 1st in early vit K deficiency
65
Q

CS and tests for vit K deficiency

A
  • CS: haemorrhage (thorax, abdomen),
  • TEST: elevated PT and PTT
  • PLT numbers and buccal mucosal bleeding time should be normal but mild thrombocytopaenia possible (d/t consumption associated with haemorrhage)
  • FDPs may be elevated
  • will see same results if animal has coagulopathy secondary to hepatic dz
66
Q

Tx - vit K deficiency

A
  • emetics, cathartics, activated charcoal if ingestion of rodenticide recent
  • transfusions of WFB or FFP to replace coagulation factors
  • may also need PRBCs to severe anaemia
  • Vit K deficiency: use vit K1 orally or PN, can give loading dose SC followed by lower dose divided q 8hrs, same dose can be given orally with a fatty meal, may take 12 hours before vit K therapy will shorten PT and decrease bleeding
67
Q

How long do you need to tx for vit K deficiency?

A
  • Warfarin or other 1st generation rodenticide; 1 week
  • 2nd/ 3rd generation rodeniticides used: need to tx for at least 3 wks, often up to 6 wks
  • check PT 24-48 hrs after last dose, if prolonged reinstate tx for another 2 wks and recheck PT
68
Q

Examples - hereditary defect of coagulation

A
  • F7 deficiency
  • Haemophilia A (F8 deficiency)
  • Haemophilia B (F4 deficiency)
  • F11 deficiency
  • F12 deficiency
69
Q

Tx - inherited coagulation defects

A
  • transfusions of FWB or plasma to replace factor deficiency and red cells
  • use of fresh or frozen plasma will give a small amount of factor
  • cryoprecipitate: 10x more factor 8 than plasma
70
Q

What is D.I.C.?

A

= disseminated intravascular coagulation

  • mixed haemostatic defect
  • results when excessive coagulation leads to widespread thrombosis
  • haemorrhage eventually results as all coagulation factors are consumed
  • not a primary event but secondary to other underlying disease (neoplasia, liver disease, I-M dz, infectious dz)
  • acute or chronic
71
Q

What are the haemostatic abnormalities with D.I.C.?

A
  • thrombocytopaenia (almost always)
  • prolonged PT and TT (commonly)
  • elevated FDPs
  • decreased fibrinogen
  • decreased AT3
72
Q

Tx - D.I.C.

A
  • stop coagulation process
  • heparin (different regimens)
  • transfusion of whole blood, plasma or cryoprecipitate as source of AT3
  • aspirin to stop PLT activation
  • correct other unerlying abnormalities
73
Q

Px - D.I.C.

A

Poor

74
Q

Summarise the general approach to the bleeding patient

A
  • PLT defect likely if haemorrhages are ecchymotic or petechiall
  • if not - coagulation defect (consider age, if v young hereditary possible, hx of toxin exposure)
  • Check CBC (PLT #)
  • evaluate HCT and PLT #s
75
Q

Summarise approach to bleeding patient if thrombocytopaenia is present

A
  • check for clots, check smear, recheck #s
  • assess degree of TP
  • PLTs approx 100*10^9/L consider haemorrhage as a cause
  • PLTs
76
Q

What should you consider if PLT #s are WNL but haemorrhages or has ecchymosis/ petechiae?

A
  • consider vWD (haemorrhages)
  • consider PLT function defects (ecchymosis or petechiae)
  • if possible check BMBT (buccal mucosa bleeding time)
  • assay for vWF Ag
  • check clotting function (PTT may be increased d/t concurrent decrease in factor 8)
77
Q

What to do if PT and PTT are prolonged?

A
  • consider vit K deficiency or DIC
78
Q

What if PTT is prolonged alone?

A

consider defects of intrinsic pathways (haemophilia A and B)

79
Q

What if PT is prolonged alone?

A

consider early vit K deficiency, liver dz, early DIC

Lymphoreticular and haematopoeitic (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions