Hemostasis

Front 1

What is hemostasis?

Back 1

The interactive process between blood vessels, platelets, coagulation proteins and the fibrinolytic system.

This process leads to the cessation of bleeding via formation and then resolution of a hemostatic plug after vascular injury.

Front 2

What are the 4 general steps that occur after vascular injury?

Back 2

1. Vasoconstriction

2. Platelet plug formation (primary hemostasis)

3. Coagulation (secondary hemostasis)

4. Clot retraction and fibrinolysis

Front 3

What triggers vasoconstriction in an injured vessel?

Back 3

Endothelin release

Front 4

Describe the formation of a platelet plug.

Back 4

This is primary hemostasis:

- Platelet adhesion and activation is triggered by exposure to subendothelial collagen and von Willebrand factor (an adhesive protein) due to damaged endothelial cells.

- vWF is on the subendothelium.

- Platelets become flattened and release their granules, which recruits more platelets and promotes adhesion.

Front 5

What clinical signs would you see in a primary hemostatic disorder?

Back 5

- Superficial hemorrhages of skin and mucosa: petechia, purpura, echymosis

- Persistent oozing from skin/surgical incisions

- Epistaxis

- Melena and hematochezia

- Subcutaneous hemorrhage

(Basically, not profuse hemorrhage)

Front 6

Name 3 disorders of primary hemostasis:

Back 6

1. Thrombocytopenia

2. Von Willebrand Disease

3. Thrombopathia (least common)

Front 7

What are possible pathologies of thrombocytopenia?

Back 7

- Decreased platelet production in the bone marrow (from neoplasia infiltrating bone marrow, drugs ie chemotherapy/estrogen/sulfa antibiotics/phenylbutazone), or infection ie BVD/distemper/parvovirus/EIA)

- Platelet destruction (usually immune-mediated thrombocytopenia, maybe idiopathic)

- Excessive platelet consumption(intravascular coagulation, vasculitis/endocarditis ie bacterial endocarditis, disorders involving hepatomegaly/splenomegaly)

- Platelet loss (blood loss - usually does not produce severe signs)

Front 8

What are the most severe causes of thrombocytopenia?

Back 8

Decreased production in bone marrow and increased destruction

Front 9

What is the most common hereditary bleeding disorder in dogs?

Back 9

Von Willebrand's disease (rare in cats, horses, cattle)

Front 10

What are thrombopathias?

Back 10

- Disorders involving platelet dysfunction

- Acquired or congenital

- Less common primary hemostatic disorder

- IE: Chediak Higashi syndrome in Persian cats and Hereford cattle; Glansmann's Thrombasthenia in Pyrenees and horses

Front 11

What will point you to a thrombopathia on a diagnostic test if you suspect a primary hemostatic disorder?

Back 11

Normal platelet count, hematocrit and vWF values

Front 12

4 tests to evaluate primary hemostasis

Back 12

1. CBC with platelet count

- <50 platelet count can cause bleeding

- Evaluate smear for giant platelets (if lots of clumps = inaccurate CBC count bc they already clotted)

2. Buccal mucosal bleeding time (BMBT)

- If normal platelet numbers, test if they are working: should take <4m to clot a small cut

- Don't perform this if you know there is thrombocytopenia! You already know it will take a long time because there are decreased platelets.

3. Bone marrow aspirate

- Helps to distinguish between IMT and a primary bone marrow disease (ie neoplasia)

4. VWF antigen assay (vWF:Ag)

- Evaluates for vWF deficiency

- <50%: considered carriers of vWD trait

- <15-25%: probably bleeding

Front 13

What clinical sign will you most likely see in a disorder of secondary hemostasis?

Back 13

- DIFFUSE hemorrhage

- Large hematomas

- Hemarthrosis

- Bleeding into body cavities

- Delayed, severe bleeding with routine surgery

Front 14

What is coagulation?

Back 14

The component of hemostasis that involves an interconnected series of enzyme-reactions that ultimately form thrombin and convert soluble fibrinogen into an insoluble fibrin plug (secondary hemostatic plug). Occurs at sites of large vessel injury.

Front 15

5 (general) things required for coagulation:

Back 15

1. Serine protease factors (cleavage enzymes thrombin, factors 7,9,10,11,12)

2. Cofactors (factor 5 is a cofactor of 10, factor 8 is a cofactor of 9)

3. Fibrinogen

4. Calcium

5. Phospholipid

Front 16

What factors are in the intrinsic pathway?

Back 16

- Factor 12 (collagen activated)

- Factor 11 (thrombin activated)

- Factor 8 (thrombin activated)

Front 17

What factors are in the extrinsic pathway?

Back 17

- Tissue factor (thromboplastin) [in vascular endothelium and platelets/WBCs and upregulated during inflammation]

- Factor 7 (activated by tissue factor)

Front 18

What factors are in the common pathway?

Back 18

- Factor 10

- Factor 5

- Factor 2 (prothrombin/thrombin)

- Factor 8

- Fibrinogen/fibrin/cross-linked fibrin

Front 19

Coagulation cascade diagram

Back 19

Front 20

Name 3 tests of secondary hemostasis, and what a positive result will tell you.

Back 20

1. ACT: activated clotting time

- Prolonged: Problem in intrinsic or common pathway

2. PT: prothrombin time

- Prolonged: problem in extrinsic or common pathway

3. aPTT: activated partial thromboplastin time

- Prolonged: Problem in intrinsic or common pathway

Front 21

Describe the ACT test.

Back 21

- Tests the intrinsic and common pathways.

- Whole blood is added to a grey-top tube that contains a contact activator.

- Keep at 37C

- Measure time for a visible clot to form (Dogs: <120s, cats and horses <180s)

Front 22

Describe the PT test.

Back 22

- Evaluation of extrinsic and common pathway.

- Performed on citrated plasma (binds calcium) using a coagulometer.

- PT corresponds to the time required to form a fibrin clot in citrated plasma after addition of an activator of the extrinsic pathway (tissue factor) and calcium.

Front 23

Describe the aPTT test.

Back 23

- In vitro evaluation of intrinsic and common pathways

- Performed on citrated plasma using a coagulometer.

- Corresponds to the time required to form a fibrin clot in citrated plasma after addition of the activator of the intrinsic pathway (ie Kaolin, silica) and calcium

Front 24

What clinical signs will you see with a secondary hemostasis disorder?

Back 24

- Large hematomas

- Hemoarthrosis

- Bleeding into body cavities

- Delayed, severe bleeding with routine surgery

Front 25

2 broad categories of secondary hemostasis/coagulopathy disorders:

Back 25

1. Coagulation factor deficiency

2. Coagulation factor inhibition (especially heparin administration)

Front 26

3 disease that will cause coagulation factor deficiency:

Back 26

1. Anti-vitamin K anticoagulant toxicity

2. Hepatic disease

3. Hemophilia

Front 27

What clotting factors do anti-vitamin K anticoagulants affect? 2 examples?

Back 27

- Affects activity of factors 2, 7, 9, 10 (the factors that need vitamin K!)

- Therefore prolongs ALL the tests!

- Bleeding usually occurs 3-7 days after exposure.

Examples:

1. Anticoagulant rodenticide toxicity (vitamin K antagonists)

- IE warfarin, bromadiolone, brodifacoum

2. Moldy sweet clover/sweet vernal grass

- Dicoumarol forms from molds

Front 28

How does hepatic disease cause secondary hemostatic disorders?

Back 28

- Causes coagulation factor deficiency

- Decreased production of factors due to decreased functional hepatic mass

- Cholestasis causes decreased vitamin K absorption and subsequent decreased production of vitamin K dependent factors

- Increases/prolongs all 3 tests

- IE: necrosis, cirrhosis, PSS

Front 29

What is Hemophilia A?

Back 29

Factor 8 deficiency, seen in dogs, cats, cattle and horses

Front 30

What is hemophilia B?

Back 30

- Factor 9 deficiency, seen in dogs and cats

- X-linked recessive disorder (there seen most commonly in males - females can be carriers and rarely have disease)

- Increased aPTT but PT is normal

Front 31

Secondary hemostatic disorders test results flow chart

Back 31

Front 32

What if you see increased activated clotting time, but PT and aPTT are both normal?

Back 32

This means there is a thrombocytopenia or thrombocytopathia (aka the coagulation cascade is fine, and the problem lies in primary hemostasis)

Front 33

What is fibrinolysis?

Back 33

- The enzymatic degradation of fibrin.

- Simultaneous with coagulation (counteractive process)

- Restores patency of vessels after hemorrhage has been controlled with a secondary hemostatic plug.

Front 34

What are the steps in fibrinolysis?

Back 34

1. Plasminogen binds fibrin in a clot.

2. Plasminogen is activated to plasmin by tissue plasminogen activator.

3. Plasmin degrades fibrin (into fibrin degradation products).

4. Free plasmin is inhibited by antiplasmin.

Front 35

How can you measure fibrinolysis?

Back 35

Measure fibrin degradation products (ie: dimers)

Front 36

What is DIC?

Back 36

Disseminated Intravascular Coagulation

- Thrombo-hemorrhagic disorder

- Always secondary to some underlying disorder

- Excessive activation of coagulation due to the presence of severe inflammatory disorder or disease

- Massive activation of primary and secondary hemostasis as well as fibrinolysis

- Mass consumption of coagulation factors, platelets and plasma anticoagulants.

- Results in diffuse deposition of thrombi at capillary level: leads to tissue ischemia and necrosis

Front 37

What is the primary trigger for DIC?

Back 37

Pathological exposure, expression or release of tissue factor (TF)

This leads to amplification of the coagulation system and excessive thrombin formation, and concurrent activation of fibrinolysis.

Results in disseminated thrombosis and hemorrhage.

Front 38

What primary diseases are associated with DIC?

Back 38

- Mostly neoplasia and systemic inflammation

Dogs: sepsis, pancreatitis, immune-mediated hemolytic anemia (IMHA)

Cats: sepsis, pancreatitis

Horses/cattle: endotoxemia, sepsis

Front 39

What clinical signs will you see with DIC?

Back 39

- Hemorrhage (petechia, ecchymoses, hemorrhagic effusions, SQ hematomas)

- Shock, multiple organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS)

- Thromboembolic disease

- Signs specific to the underlying disease

Front 40

How can you test for DIC?

Back 40

There is no test for it!

You can diagnose by looking for laboratory abnormalities consistent with DIC:

- increased PT and aPTT

- thrombocytopenia

- decreased antithrombin

- increased D-dimer

Also will see:

- Presence of an underlying cause/disease

- Clinical signs of hemorrhage and/or thrombosis