Laboratory Evaluation of Hemostasis part I

Marrow disease thrombocytopenia

Due to:

Drugs(chloramphenicol, sulfa) toxins

Infections: BVD, canine distemper, Parvovirus

Estrogen, bracken fern poisoning

Suspect Thrombocytopenia due to marrow disease?

A. Start off with a blood smear and look for signs of Thrombopoiesis

B. Definitive diagnose via bone marrow aspirate

What are signs of Thrombopoiesis?

Large platelets (Large- reactive/immature)

Macrothrombocytopenia is inherited by what dog breeds?

Cavalier

Norfolk terrier

What species is known to clump?

cats

cows

Causes of thrombocytopenia: Abnormal distribution(sequestration)

Spleen enlargement

Liver disease

Causes of thrombocytopenia: Idiopathic or multifactorial

combined decreased production and survival

Causes of thrombocytopenia: decreased survival

Increased destruction

Increased consumption

Causes of thrombocytopenia: decreased production

Inadequate megakaryocyte production

Bone marrow disorders

What answer best matches the image?

Thrombocytopenia

Macrothrombocytopenia is inherited by what species?

cats

What leads to clumping?

Delayed transferring from syringe to tube

Inadequate mixing

Old samples > 5 hrs

The two causes of pseudothrombocytopenia

Large platelets and Platelet clumping

Decreased survival → spleen

increased Destruction

Ab-mediated

Idiopathic

Increased Activation &/or consumption → blood vessels

Vasculitis

DIC(disseminated intravascular coagulation)(intravasc. Consumption)

Endotoxins

Sequestration

Reversible(hypothermia)

or

Irreversible(Endotoxins) pooling in the lungs

Pathogenesis of Immune-mediated Thrombocytopenia (IMT)

Can be seen with IMHA

Formation of anti-platelet antibodies → Macrophages engulf the antibody-coated platelets→ Thrombocytopenia

Pathogenesis of Immune-mediated Thrombocytopenia diagram

Pathogenesis of consumptive thrombocytopenia

Damage to the endothelium> activation of platelets> platelet aggregation

Platelet activation and aggregation→ consumption and removal from the blood→ Thrombocytopenia

A dog’s CBC results included a mild leukocytosis, mild anemia with schizocytosis, keratocytosis, and thrombocytopenia (100,000/μL; RI 150,000–450,000). The thrombocytopenia was likely due to:

B. Intravascular consumption of platelets

Infectious Canine Cyclic Thrombocytopenia(anaplasmosis)

Pathogenesis: probably immune-mediated destruction or sequestration

Agent: Anaplasma platys

Vector: Ticks

Cyclic aspects: peak parasitemia followed by thrombocytopenia

Agent: Anaplasma platys

Marked thrombocytopenia causes…

hemorrhage

Typically [platelet] < 20,000/μL

Hemorrhage does not typically = Thrombocytopenia

Does blood loss cause thrombocytopenia?

Usually not, Only marked blood loss →mild thrombocytopenia.

(should have concurrent anemia & hypoproteinemia)

Will not spontaneously bleed unless they are less than?

20,000 uL

Thrombocytosis (Primary or secondary)

Definition: [Plt] > appropriate upper reference limit [URL]

1. Increased production or 2. Redistribution

Increased production can be?

clonal/non-clonal

Clonal: Primary(cancer)

Rare* [Hemic neoplasia] / Acute megakaryoblastic leukemia

> 2x URL: If extreme thrombocytosis > 1,000,000/μL Bleeding/Clots (decreased function)

URL

upper reference limit

Non-clonal: Secondary(non-cancerous)

As a reaction to other conditions [Reactive Thrombocytosis]

≤ 2x URL

Increased production (Reactive Thrombocytosis) causes

*Inflammation (infection, immune mediated) IL-6 stimulates Thrombopoietin(Tpo)

*Iron deficiency

*Recovery from thrombocytopenia- Rebound Thrombocytosis

*Post- Splenectomy

2. Redistribution

Exercise

Epinephrine

Summary Hemostasis 3 stages

The receptor for vWf (adhesion) is

GPIb

The receptor for fibrinogen (aggregation) is

GpIIb/IIIa

Deficiency in GpIIb/IIIa is

glanzmann thrombasthenia

seen in otterhounds, great pyrenees, and horses

Deficiency of vWB factor

Von Willebrands disease

doberman pinscher

COAGULATION CASCADE simplified

Why is it important to divide 1’ & 2’?

Types of bleeding differ(sometimes you can guess the system affected based on clinical signs)

Lab tests usually evaluate either 1’ or 2’ hemostasis

DDx are different depending on which part of the coagulation cascade is affected

CLINICAL APPROACH Determine:

If the bleeding is the result of a defect or local tissue disease?

If there is a defect, localize it → Narrow DDx list

For primary hemostasis to occur you need…

1) Normal subendothelium [disorders are rare]

2) Adequate #s of platelets

3) Normal platelet function

4) vWf

5) Fibrinogen [ can be 1’/2’][rare]

Any 1’ defect…Your DDx..

1. [Plt] adequate?? → 1) Thrombocytopenia

2. vWF??? → 3. Abnormal plt function(receptor deficiencies)

3. Normal PLT function (receptors!) ???→ 2. vWf deficiency

Big point is for 1’ hemostasis need…

Therefore for 1’ disorders the DDx list would be:

1) Thrombocytopenia → 4 factors

2) vWf deficiency → %

3) Abnormal plt function(receptor deficiencies)

Intrinsic 12,11,9 & 8 Walmart analogy

Why pay $12 when you could pay 11.98

Extrinsic factor 7

Has the shortest half-life

Good screening test

test extrinsic and common

Secondary hemostasis =

Primary hemostasis =

muscosal bleeding

Clinical signs: Primary

Petichiae- Thrombocytopenia/vasculitis(pinpoint hemorrhages)

Mucosal bleeding

Clinical signs: secondary

Large hematomas/SQ bruising- usually but not specific

Cavity bleeding: hemoabdomen, hemothorax, hematerosis

Frank hemorrhage

Clinical signs: non-specific

can be both 1’/2’

Excessive bleeding following surgery/venipuncture

Ecchymoses(paint brush style hemorrhages)

What 3 broad differentials should be considered for 1’ hemostatic disorders?

1) thrombocytopenia

2) vWf deficiency

3) abnormal platelet function

Morphology(microscopy) comments

No platelet clumps at feathered edge/body of smear

[Plt] is inadequate; manual count= 0-1 plt/hpf