Circulatory Disturbances - Hemorrhage & Thrombosis

Pathology - Lec 13 - Exam 2

What are the 2 disorders of hemostasis?

1. hemorrhage → extravascular blood loss

2. thrombosis → inappropriate formation of intravascular clots

What are the 2 mechanisms of hemorrhage?

1. hemorrhage by rhexis → ruptured vessel

2. hemorrhage by diapedesis → RBC squeeze through intact vessel walls

T/F: The appearance of hemorrhage depends on cause, location, and severity.

TRUE

Hemorrhage is characterized by what?

size

What are the 3 different classifications of hemorrhage based on size (from smallest to largest)?

1. petechia → 1-2 mm

2. purpura → 3 mm - 1 cm

3. ecchymosis → 1-3 cm

What is suffusive hemorrhage?

larger contiguous areas of hemorrhage

hematoma

occurs in a focal, confined space

A hematoma grows until what?

pressure exerted by extravascular blood matches the pressure of blood within the injured vessel or the vessel is sealed by hemostasis

T/F: Hematomas are always life-threatening.

FALSE - can be insignificant or rupture & potentially cause death

Which classifications of hemorrhage have a diapedesis mechanism?

petechiae & ecchymoses

What are the 2 major causes of hemorrhage by diapedesis?

1. minor defects in otherwise intact blood vessels (endothelial damage)

2. defects in 1^o hemostasis (platelet defects, von Willebrand disease)

What are the 2 major causes of hemorrhage by rhexis?

1. trauma

2. extensive damage to vessel integrity by infectious agent (invasive fungi)

Hemorrhage occurs due to abnormal function or integrity of what?

• endothelium and blood vessels

• platelets

• coagulation factors

What are the causes of hemorrhage via blood vessels?

• trauma

• inflammation

• infectious disease

• genetic disorders

• nutritional disorders

Hemorrhage in relation to blood vessel trauma is caused how? Examples?

physical disruption of blood vessel wall

ex) subdural hematoma, aural hematoma, iatrogenic hemorrhage (surgery)

What is an example of blood vessel hemorrhage due to inflammation?

Feline Infectious Peritonitis (FIP) → type III hypersensitivity rx (FIV also type IV)

What is an example of blood vessel hemorrhage due to infectious disease?

epizootic hemorrhagic disease → vasculitis & hemorrhage due to endothelial injury

What is an example of blood vessel hemorrhage due to genetic disease?

Ehlers-Danlos Syndrome/ Dermatosparaxis → hereditary collagen dysplasia (fragile skin ± blood vessels)

What are is nutritonal disorder that can lead to blood vessel hemorrhage?

Vitamin C deficiency → scurvy

What purpose does ascorbic acid (vit C) serve?

serves as an enzyme cofactor

Species such as guinea pigs, primates, cetaceans, some bats, birds, and fish require a _________ source of Vitamin C. Why?

dietary

deficiency of L-gulonolactone oxidase (coverts L-gulonolactone to L-ascorbic acid)

Ascorbic acid serves as an enzyme cofactor for what? What are these required for?

prolyl and lysyl hydroxylases

required for the hydroxylation of proline & lysine during procollagen synthesis

What does a deficieny in hydroxylysine and hydroxyproline cause?

impaired function of intermolecular collagen cross-links

A vitamin C deficiency causes what?

deficient & defective collagen synthesis → bone, connective tissue, blood vessels (capillary fragility)

Vitamin C is also required for the synthesis of which important substances?

dopamine, norepinephrine, epinephrine, carnitine, wound healing, conversion of cholesterol into bile acids. antioxidant

What 2 platelet issues can cause hemorrhage?

1. decreased platelet numbers

2. abnormal platelet function

thrombocytopenia

decreased numbers of platelets

What are some things that can cause thrombocytopenia?

decreased production

increased destruction

increased use

Decreased production of platelets leading to hemorrhage is due to what? Examples?

megakaryocyte damage or destruction

radiation, estrogen toxicity, cytotoxic drugs, viral diseases (parvo)

Increased destruction of platelets leading to hemorrhage is due to what? Examples?

immune mediated 

drug rxn, viral diseases (EIA)

Increased use of platelets leading to hemorrhage is due to what? Examples?

diffuse endothelial damage or generalized platelet activiation

DIC

thrombocytopathy

decreased function of platelets

hereditary thrombocytopathy

deficiency of surface receptors → von Willebrand disease

acquired thrombocytopathy causes

NSAIDS (aspirin)

renal failure → uremia

Cause of hemorrhage?

decreased concentration of coagulation factors

Decreased concentration of coagulation factors can either be ________ or __________.

hereditary

acquired 

What are the 2 categories of acquired coagulation factor decrease?

1. decreased production

2. increased use

What are the hereditary coagulation disorders?

X-linked hemophilias (A & B)

autosomal factor deficiencies

T/F: Clincial signs vary with hereditary coagulation disorders.

TRUE

Causes of decreased production leading to acquired coagulation disorders?

liver disease (dec synthesis)

vitamin K deficiency (dicumarol in moldy sweet clover, warfarin, sulfaquinoxaline)

Causes of increased use leading to acquired coagulation disorders?

disseminated intravascular coagulation (DIC)

thrombosis =

mechanisms involved in the formation of a thrombus in an injured blood vessel

thrombus

an aggregate of platelets, fibrin, & other blood elements formed on a vascular wall

What are the 2 types of thrombi?

1. physiological → normal hemostasis, rapidly resolved

2. pathological → persistent or inappropriate

What is Virchow’s Triad?

1. vascular injury → inflammation

2. altered blood flow → stasis or turbulence

3. hypercoagulability → inherited or acquired

T/F: Alterations to endothelium (vascular injury) is the most important of aspect of Virchow’s Triad in vet med.

TRUE

What are the possible alterations to the endothelium leading to vascular injury?

increased production of procoagulant substances

decreased production of anticoagulant substances

What are some causes of vascular injury?

trauma, vasculitis, metabolic disorders, neoplasia

What happens when the endothelium is injured?

• exposure of subendothelial collagen

• release of TF (III)

• platelet adherence & activation

• local depletion of prostacyclin and tissue plasminogen activator

normal laminar blood flow

cells flow centrally in the blood vessel separated from the endothelium by a thin layer of plasma

How does normal blood flow affect platelets?

keeps platelets away from endothelium preventing them from sticking

What can lead to stasis of blood flow?

heart failure (systemic)

vascular obstruction or dilation (local)

Slow rate of blood flow favors what?

• accumulation of activated CoAg factors

• contact of platelets with the endothelium

T/F: Turbulence does not disrupt laminar blood flow.

FALSE

What does turbulence favor?

• platelets interacting more with the endothelium

• mixing of blood = more CoAg factor interaction

• physical damage/ activation of the endothelium

When is turbulence the greatest?

• where vessels branch

• at a narrowing of the vessel lumen

• at sites of venous or lymphatic valves

Hypercoagulability reflects what?

an increase or decrease in the concentration of activated hemostatic proteins

What are the 2 categories of hypercoagulability?

1. increased activation

2. decreased degredation

What is the most common cause of hypercoagulability?

INFLAMMATION

also: stress, surgery, neoplasia, pregnancy, renal disease

How does renal diease contribute to hypercoagulability?

loss of Antithrombin III and Protein C & S

What determines the gross appearance of thrombi?

dependent on underlying cause, location, & composition

What is the key point regarding thrombi?

they are ALWAYS attached to the vessel/ heart wall

The shape and appearance of arterial thrombi is determined by what?

rapid flow in arteries/ heart

Arterial thrombi are usually initiated by what?

endothelial damage → point of attachment

Arterial thrombi are composed primarily of what?

platelets and fibrin

Gross appearance of arterial thrombi:

dull, tan to red-gray

± vessel occlusion

tail extends down stream

laminated appearance

Lines of Zahn

alternating layers of platelets, interspersed by fibrin intermixed with erythrocytes and leukocytes

T/F: Lines of Zahn are characteristic of venous thrombi.

FALSE - arterial thrombi

Venous thrombi often occur where?

in areas of stasis → increased activation of CoAg factors + reduced clearance

Low blood flow allows incorporation of _______ into a venous thrombus.

RBCs

What makes up a venous thrombus?

loose meshwork of platelets, fibrin, RBCs, and WBCs

gross appearance of venous thrombi:

gelatinous, soft, glistening

dark red

almost always occlusive → molded to wall

often extend upstream from point of origin

T/F: The point of origin of venous thrombi may be difficult to determine.

TRUE

Characteristics of postmortem clots:

softer

do NOT have point of attachment

do NOT have associated lesions

Gross appearance of postmortem clots:

current jelly: dark red

chicken fat: yellow

Significance of a thrombus is determined by what?

location & ability to disrupt perfusion in a dependent tissue

Significance of a thrombus based on size:

small vs large

non-occlusive vs occlusive

Significance of a thrombus based on rate of formation:

slow vs fast

Other determinants of thrombi significance:

method of resolution or repair

number of vessels affected