Clinical Pathology - Coagulopathy

Front 1

function of vWF ?

Back 1

activates platelet aggregation

Front 2

vWF released during primary or secondary hemostasis?
From where?

Back 2

primary (platelet plug formation)...released from damaged subendothelial cells

Front 3

Is fibrin accumulation part of primary or secondary hemostasis?

Back 3

secondary

Front 4

what 3 pathways of secondary hemostasis?

Back 4

1. extrinsic
2. intrinsic
3. common

Front 5

Which secondary hemost. pathway is plasma based and slow?

Back 5

INTRINSIC
*gets name b/c factors originate from "inside" vessel!

PIS (plasma intrinsic slow)

Front 6

Which pathway (intrinsic or extrinsic) of clot form. is faster and more powerful?

Back 6

EXTRINSIC SYSTEM (tissue-based)
is only 15-30 second long.

~in contrast, Intrinsic system (plasma-based) takes 1-6 min

E_ Too Fast

Front 7

Which secondary hemost. pathway is tissue based and rapid?

Back 7

extrinsic

Front 8

Which pathway includes F11,12 contact factors b/c activated by contact with other factors INSIDE injured blood vessel??
(also factors 8,9 involved)

Back 8

intrinsic (plasma based and slow)

"Why stay inside (intrinsic) and pay $11.98 or $12,
when can go outside (extrinsic) and pay only $7?"

Front 9

Which pathway includes factors 10,5,2,and 1?

Back 9

common

hint: divide each factor by 2 to get next one

Front 10

What happens during common pathway?

Back 10

converts prothrombin to thrombin & forms cross- linked fibrin
(where 2 arms of Y come together)

Front 11

4 parameters for testing Hemostasis

Back 11

1. Platelets counts
2. (Mucosal) Bleeding Time / in vivo
3. OSPT = 1 Stage Prothrombin Time
4. APTT = Activated Partial Thromboplastin Time

Front 12

APTT stands for?

measures ?
normal APTT time?

Back 12

- Activated Partial Thromboplastin Time (name doesn't make a whole lot of sense, b/c thromboplastin is TF of extrinsic system)
- measures INTRINSIC and common pathway

expected time 60-120 sec

AI

Front 13

OSPT stands for?

measures ?
normal OSPT time?

Back 13

OSPT = One Stage Prothrombin Time

-> measures EXTRINSIC and common pathways (expected time < 10 sec!)

OE memory trick: Obama Elected '10 (2010)

Front 14

The INTRINSIC SYSTEM is plasma-based pathway. During first stage of clot formation, WHAT FACTOR is activated initially by change in surface charge of endothelial membranes?
What are some stimuli/injuries that can stimulate this? Is bleeding always involved?

Back 14

Change in surface charge of endothelial membranes activates **Plasma Factor XII**
e.g. caused by inflammatory reactions (endotoxins); activated platelets; contact with glass surface (bleeding not necessary!)

Front 15

Is Factor XII a plasma or platelet factor?
F12 activates a cascade of enzyme involved in intrinsic pathway. Name these 3 enzymes.

Back 15

Plasma Factor, of plasma-based INTRINSIC SYSTEM

*activates an enzymatic cascade factors XI, IX, VIII of intrinsic
then continues onto common pathway

Front 16

What is another name for Thromboplastin?
What pathway is it part of?
Function?

Back 16

Tissue Factor (TF3) aka Factor 3 --> of EXTRINSIC PATHWAY = unique b/c released by injured tissue outside circulation e.g. subendothelial cells

>once reaches plasma, quickly binds to factor 7 + calcium then enzymatic cascade continues onto common pathway (X, V, Ca) leading to PAC

Front 17

COMMON pathway begins when ?

Back 17

EXTRINSIC and/or INTRINSIC pathway, each produces unique factors capable of activating Prothrombin-Activator Complex.

COMMON pathway begins with Factor X (along with Factor 5) form Prothrombin-Activator Complex which converts Prothrombin (F2) to Thrombin (F2a)
(represent merger of ext/intrinsic pathways)

Front 18

Again name 4 factors of common pathway!

Back 18

10 (hageman factor),
5,
2 (prothrombin),
1 (fibrinogen)

Front 19

APTT measure?
what is contact activator added to tube/sample?
what factors added?
expected time?

Back 19

APTT = Activated Partial Thrombo- plastin Time
- measures INTRINSIC and common pathway <- measures clot formation after clean venipuncture in citrated tube and addition of contact activator (diatomaceous earth), Platelets Factors and Calcium
(expected time 60-120 sec)
A60

Front 20

OSPT

expected time?
what is added?

Back 20

1 Stage Prothrombin Time:
-> measures EXTRINSIC and COMMON pathways
(expected time < 10 sec)

- measures clot formation in citrated plasma after addition of Tissue Factor, Platelet Factors and calcium

One 10

Front 21

Which is tissue-based pathway during stage 1 of clot formation?

Back 21

EXTRINSIC SYSTEM: comes from outside blood vessel, membrane disrupted

Injured tissue expresses
Tissue Factor (factor 3)

Front 22

(Mucosal) Bleeding Time

what does it test?

Back 22

TESTS PLATELET PLUG FORMATION (not clotting)
*stop time until bleeding stops after standardized small incision into
skin or mucosa (expected time 1-5 min)
-> measures functional ability of platelets and vMF to plug minute injuries

Front 23

What is Tissue Factor?

What is it part of?
What does it activate?

Back 23

Injured tissue Factor (Thromboplastin), of extrinsic pathway, activates an enzymatic cascade (factors VII, X, V, Ca) leading to P.A.C

note: extrinsic comes from outside blood vessel, membrane disrupted

Front 24

Which is most important enzyme of clot formation depends relies of vitamin K?

Name Vit K antagonist..what does it cause?

Back 24

Factor 7 (most important, b/c shortest HL so conseq. of absence apparent sooner), Prothrombin

Coumarin = Vit K antagonist -> impairs liver synthesis of several clotting factors incl. Prothrombin

Front 25

SYNTHESIS of prothrombin, a hepatic alpha globulin, is dependent on ? (~two words)

Attaches itself to ?

Back 25

- its liver synthesis is **VITAMIN K** dependent (was not asking about activation!)

-attaches itself to activated platelets

Front 26

What polymerize into long fibers and X-link into meshwork w/i and around the platelet plug?

Bonus: what is time frame?

Back 26

FIBRIN, this meshwork = STABLE CLOT

-> bleeding stops
(within 3-6 min after injury)

Front 27

How is FIBRIN formed?

Back 27

Thrombin hydrolyses FIBRINOGEN (=hepatic soluble protein; already bound to activated platelets) into FIBRIN monomers

Front 28

The INTRINSIC SYSTEM is plasma-based pathway. During first stage of clot formation, WHAT FACTOR is activated initially by change in surface charge of endothelial membranes?
What are some stimuli/injuries that can stimulate this? Is bleeding always involved?

Back 28

Change in surface charge of endothelial membranes activates **Plasma Factor XII**
e.g. caused by inflammatory reactions (endotoxins); activated platelets; contact with glass surface (bleeding not necessary!)

Front 29

CLOT RETRACTION

Back 29

W/i the next 30 minutes after stable clot (fibrin meshwork around plug), platelets contract more and pull fibrin threads together
-> clot tightens and pulls edges of injured blood vessel together

Front 30

Fibrinolysis

what is it?
time rame?
enzymes involved?

Back 30

Hemostasis: Fibrinolysis = removal of clot (1-2 days after clot formation)

tissue-Plasminogen Activator = tPA
activates hepatic plasma factor Plasminogen to PLASMIN = proteolytic enzyme
- plasmin nibbles at fibrin fibers

Front 31

PLASMIN

Back 31

PLASMIN = proteolytic enzyme

- plasmin hydrolyses fibrin fibers + clotting factors! into FDPs (Fibrin Degradation Products);

Front 32

FDPs are removed by

Back 32

Fibrin Degradation Products are removed by macrophages

Front 33

- _____ inhibit platelets adhesion


- secreted by ??

Back 33

PROSTACYCLIN and Nitric Oxide -> inhibit platelets adhesion

secreted by intact endothelial cells and WBC

Front 34

What limits fibrin formation and positive feedback?

Back 34

Fibrin binds Thrombin -> limits fibrin formation and positive feedback

(remember normally thrombin hydrolyzes fibronogen to form fibrin monomers, as well as +f/b of int/ext.systems)

Front 35

* ANTI-THROMBIN III

* ______from ____ combines with Anti-thrombin III and greatly augments its effectiveness

Back 35

ANTI-THROMBIN III (α globulin) deactivates Thrombin and other clotting factors

Heparin from Mast Cells / Basophils increases A-TIII's effectiveness

Front 36

In vitro anticoagulation

Back 36

Calcium binding agents (e.g. citrate, oxalate, EDTA), heparin

Front 37

In vivo anticoagulation

Back 37

Heparin, Vit K antagonists, prostaglandin synthesis inhibitors (NSAIDs)

Front 38

Why does calcium help with clotting?

Back 38

Most clotting factors negatively charged, so Ca+2 helps bring in.

Front 39

Thrombocytopenia

Back 39

decreased production (bone marrow; drugs; FeLV) or increased destruction (immune-mediated) or consumption

Front 40

von Willebrand’s Disease (Form I,II,III)

Back 40

= most common bleeding disorder in animals due to genetic lack / insufficiency of vWF -> platelets fail to adhere to injury sites -> spontaneous bleeding (or ); clinical signs can be mild / severe / fatal; described in ca 60 breeds of dogs with highest
prevalence in Dobermans

Front 41

Vit K deficiency / Rodenticide poisoning

Back 41

Coumarin = Vit K antagonist -> impairs liver synthesis of several clotting factors incl. Prothrombin

Causes hemorrhagic anemia, regenerative so macrocytic, hypochromic, reticulocytes up, PP down, APTT prolonged, OSPT prolonged

Front 42

Thrombopoietin

Back 42

Hormone produced mainly by liver and kidney that regulates production of platelets by bone marrow; stimulates production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets

Front 43

primary hemostasis

Back 43

blood vessel constriction & platelet aggregation/adhesion

Front 44

secondary hemostasis

Back 44

coagulation cascade

When clot has stopped bleeding & blood vessels repair, tertiary hemostasis ->fibrinolysis -> perfusion restored.

Front 45

tertiary hemostasis

Back 45

fibrinolysis --> perfusion restored.

Front 46

T/F: Usually 70-80% clotting factor/platelet loss is needed to cause bleeding - may occur spontaneously – may occur after minor injury eg teething, minor trauma or surgery

Back 46

True: Usually 70-80% clotting factor/platelet loss is needed to cause bleeding

Front 47

T/F Coagulopathy is possibly hereditary in young animals

T/F: Coagulopathy can be acquired in older animals, from exposure to drugs or poisons

Back 47

True : Coagulopathy is possibly hereditary in young animals, & possibly acquired in older animals, from exposure to drugs or poisons – do check history carefully.

Front 48

12,11,9,8 part of?

Back 48

intrinsic

Front 49

Factor 1 =

Back 49

F1 = prothrombin

Front 50

Factor 4 =

Back 50

F4 = calcium

Front 51

kind of tube used for coagulation test (OSPT/APTT)?

Back 51

Sodium citrate (blue)

Front 52

kind of tube used for coagulation test for platelet count?

Back 52

EDTA (purple)

Front 53

prolonged OSPT indicates?

Back 53

Problem with extrinsic pathway:
Vitamin K problem, advanced liver disease, or DIC

Front 54

prolonged APTT indicates?

Back 54

deficiency of factors VIII & IX, by heparin toxicity, angiostrongylus infestation and rarely by liver disease

Front 55

If the mean platelet volume is raised, what could this indicate?

Back 55

increased platelet production, especially in immune mediate thrombocytopenia

Front 56

What is a crude test for platelet function and helps to detect thrombocytopathy?

Back 56

clot retraction time

Front 57

What does increased values of fibrinogen assay indicate?

Back 57

inflammation in large animals, especially cattle

Front 58

If clot lysis test results in lysis of clot in less than 24 hrs. than indicates?

Back 58

excess plasmin

Front 59

A defect in what tends to cause capillary bleeding with petechiae & ecchymoses in skin or mucosa over a period of time?

Back 59

primary hemostasis

Front 60

A defect in what tends to cause sudden, often severe bleeding into muscles, body cavities, eyes or joints, or into the gut or urinary or respiratory tract?

Back 60

secondary hemostasis

Front 61

What are the most common cause of coagulopathies?

Back 61

platelet disorders and rodenticide poisoning

Front 62

What syndrome occurs when severe inflammation or endotoxemia, necrosis, neoplasia, septicemia, viremia, or parasitemia, damage blood vessels, strip endothelium & bare the underlying collagen & cause multiple thrombi?

Back 62

disseminated intravascular coagulation

Front 63

What is the diagnostic test of disseminated intravascular coagulation?

Back 63

Fibrin Degradation Products present
FDPs formed plasmin digests fibrin; incr. fibrinolyisis indicates incr. coag.!

Front 64

Vitamin K is essential in production of what factors?

Back 64

2,7,9, and 10 (7 is the most important and has short HL)

Front 65

What is usually caused by ingestion of warfarin and other rodenticides (brodifacoum and "storm")?

Back 65

vitamin K deficiency

Front 66

How would vitamin K defic. be diagnosed?

Back 66

prolonged OSPT, defic. in factor 7, mild prolongation of APTT and ACT tests

Front 67

What factor affected in hemophilia A in dogs, cats, and horses?

Back 67

factor 8

Front 68

deficiency in christmas factor in dogs and cats refers to what clotting factor?

Back 68

factor 9

Front 69

What factor defic. occurs in friesian cattle and dogs?

Back 69

factor 11

Front 70

What animals does the Hagemann Factor (factor 11) occur in?

Back 70

cats

Front 71

For emergencies (horse with major blood loss) where don't know blood type, what blood groups should DONOR be negative for?

Back 71

Aa and Qa negative

but i thought horses don't develop alloantibodies (Ab to blood/tissue for other of same species)???

Front 72

These animals have 11 blood groups, but B & J are most important. Transfusion reactions are rare but it is best to give blood from a J-negative animal?

Back 72

cows

Front 73

What animals have 8 blood types, but DEA 1.1 and 1.2 are the most antigenic, also have no naturally occuring antibodies, so first transfusion without X matching should be safe?

Back 73

dogs

Front 74

cats have what blood groups?

which type develops strong allo-ab against the other?

Back 74

has blood groups A, B, and AB (rare).

B has strong Anti-A alloantibodies, (A has weak anti-B alloantibodies)

Front 75

In America >95% of cats are in what blood group? Europe?

Back 75

A in US; in Europe most cats are group B

Front 76

What breeds of cat are more likely to be bloodgroup B? (4)

Back 76

abyssinian, birman, maine coon, persian

Front 77

How often can dogs donate blood?

Back 77

every 3-4 weeks
(15 ml / kg BW each time)
~300 ml

Front 78

Describe an ideal equine donor?
What dz must be negative for?

Back 78

weight at least 1000 pounds, have normal PCV and plasma protein, tested for equine infectious anemia, and not have had a blood transfusion or a FOAL!

Front 79

What should be given if there is severe edema?

Back 79

albumin; PP loss in circ. leads to reduced osmotic pressure in vessels

Front 80

Can transfuse blind in what species?

Back 80

dog (except stray dogs) & cow,

Front 81

What is caused by fungal proliferation on mouldy clovers, and releases a form of coumarin? Consequence of this?

Back 81

"sweet clover" poisoning; Vit. K poisoning = bye bye factor 7

Front 82

8.)Which of following most accurately describes function of tPA?
A. Inhibition of platelet aggregation
B. Degradation of factors 5 & 8
C. Inactivates Thrombin, Plasmin, Kallekrein, and a few other clotting factors
D. Catalyzes Plasminogen activation during fibrinolysis
E. All of the above

Back 82

8. (D) is correct – tPA or tissue Plasminogen activator converts Plasminogen -> Plasmin -> degrades Fibrin -> releases FDPs!
Wrong answers: A. Inhibition of platelet aggregation by PGI2 and NO B. Degradation of factors 5 & 8 actually negative feedback from thrombin itself C. Are functions of ATIII

Front 83

6.)Which of following is NOT one of three most common causes of severe thrombocytopenia? (more than one answer possible)
A.IMTP
B.Ehrlichia
C. Disseminated intravascular coagulation (DIC)
D. Anaplasma
E. von Willebrand’s Disease

Back 83

D, E

Front 84

4.) Which of following is most likely to get Hemophilia A?
A. Female doberman
B. Male Jack Russell Terrier
C. Female german sheperd
D. Male springer spaniel

Back 84

4.) B. Male Jack Russell Terrier
- Sex-linked (males only)
- Jack Russell Terriers
- German shepherds

Front 85

True or False: ACT will always be prolonged if APTT is prolonged, but some animals with “normal” APTT have prolonged ACT.

Back 85

False: Both ACT & APTT evaluate intrinsic & common clotting mechanisms. But APTT is MORE sensitive than ACT. (ACT only screening test.) Therefore, APTT will always be prolonged if ACT is prolonged.

Front 86

Why might nephropathy lead to excessive coagulation elsewhere in body? (be specific)

Back 86

Loss of Anti-Thrombin III thru glomerulus (PLN)