Week 11 Pre-work

Bone marrow

become mature erythrocytes

Blood

deliver oxygen to tissues

Spleen

reserve for RBCs

macrophages in the spleen destroy old RBCs

Iron kinetics in healthy animals

1) intestine absorption;

2) transported in plasma bound to transferrin; apotransferrin + Fe → transferrin

Fe binds…

ferritin in rubricyte then incorporated into hemoglobin

Iron is stored where?

stored in marrow, spleen, and liver as hemosiderin, ferritin

Hypoferremia

low iron in serum or plasma

Hypoferritinemia

low ferritin in serum or plasma

Two important important conditions that lead to hypothermia

iron deficiency and inflammation

transferrin: negative acute phase protein

inflammatory cytokines cause liver to decrease production of transferrin

hypoferremia: persistent low-grade blood loss(intestine or skin)

loss of RBCs with iron rich hemoglobin →

stored iron used to produce more hemoglobin for RBCs →

eventually, depleted total body iron content →

decrease in stainable iron in marrow/spleen

Hypoferremia: persistent inflammatory disease

Cytokines(IL-6) promotes synthesis of hepcidin →

hepcidin internalizes iron in macrophages membranes →

iron stays in macrophages →

increase in stainable iron in marrow/spleen

Erythrocyte Analytes of the Complete Blood Count (CBC)

PVC, Hct, Hgb, and RBC all measure?

RBC mass

decreased RBC mass= anemia

Hematocrit

Proportion of RBCs per blood volume

Hemoglobin

reflects oxygen carrying capacity of blood

Hgb x 3 = Hct

MCHC(mean cell hemoglobin concentration) =

Hgb x 100 / Hct

Platelet or thrombocyte:

Cellular fragment of a megakaryocyte that participates in the first hemostasis step

Fibrin:

Is the active form of factor I; it is a sticky, threadlike protein that “glues” together the cells and clotting factors in a blood clot

Thrombopoietin:

A liver protein that is the primary regulator of megakaryocyte development and platelet production

endothelial cells have a dynamic interaction with?

Platelets

they regulate the activation of platelets in both intact and injured vessel walls

An intact endothelium prevents?

the adhesion of platelets through the release of nitric oxide and prostacyclin

Following a vessel injury, activated endothelial cells will release what molecules?

vWF, Tissue plasminogen activator(tPA), and endothelin-1 and express a variety of surface receptors that increase platelet cell adhesion

Activated endothelial cells favor…

the formation of thrombin, which stimulate blood clotting

Platelets will release a variety of molecules…

Serotonin and thromboxane A2 and platelet plug formation(Prothrombotic molecules ADP and thromboxane A2)

After activation platelets bind to

exposed factors in the injury site, vWF and collagen

vWF(GP1B) receptors

receptors on platelets that bind to the vWF which have bound to the exposed collagen molecules and platelets are activated

Alpha granules(in platelets)

release additional vWF and platelet derived growth factor for clotting

Dense granules(in platelets)

release ADP(binds to P2y12) and thromboxane(binds to TP) which bind to other platelets

Fibrinogen

linking molecule which adheres to other platelets and makes platelet aggregation

The enzymes in the 3 pathways are which by which cofactors?

Ca, phospholipids, and Factor V

Fibrinolysis

process that involves the activation of proteolytic enzymes which aims to degrade the fibrin clot

Process of fibrinolysis

endothelial cells release tissue plasminogen activator(tPA) →

tPA activates plasminogen →

plasmin degrades fibrin, and the clot dissolves

factor Xa

activates thrombin to recruit more platelets

Thrombocytopenia refers to a

platelet concentration below the lower reference interval, in this case 150,000

most common cause of bleeding

Inaccurate platelet count due to cell size

large platelets; miscounted as RBCs or excluded

Pseudothrombocytopenia

Due to platelet clumps/clots

large platelets(cats) and cavaliers and norfolk terriers

Platelet graphs

Ski slope is healthy

bumpy when clumping

upward trend: large platelets

Adequate platelets

About 1 platelet per 30 RBCs, 8-10/hpf in a healthy dog or cat

Pathogenesis of thrombocytopenia

1) decreased production

2) decreased survival(increased survival and consumption)

3) abnormal distribution(sequestration)

4) Idiopathic or multifactorial(decreased production and survival)

Tests for intrinsic and common pathway

Activated clotting time(ACT), Partial thromboplastin time(PTT)

Tests for extrinsic and common pathway

prothrombin time(OSPT,PT)

Activated clotting time(ACT) test

screening test, tests most of the coagulation pathway

activates the intrinsic and the common pathway

normal dogs <90s, cats <165s

For ACT severe thrombocytopenia <10,000/ul can cause?

mild prolongation of ACT

APTT test

evaluates intrinsic and common pathways

more sensitive than ACT

ran using plasma rather than whole blood

Process of APTT test

reagent and calcium → added to plasma

Goal of the three pathways

Thrombin(II) → fibrinogen(I) → fibrin

PT/OSPT test

similar to PTT

Key points for PTT/PT

if the citrate tube is underfilled → excess anticoagulant and artificial prolongation of PT/PTT

FDPs are

any of the many protein fragments that can be produced when either fibrinogen or fibrin is cleaved by plasmin

D-dimers are

a specific sub-set of FDPs

can only be formed by the breakdown of cross-linked fibrin and not fibrinogen

FDPs/D-dimers are a marker for

thrombotic disease

Increased concentrations are not 100% specific for thrombotic disease but…

the higher the concentration the more likely its due to thrombosis

Disseminated intravascular coagulation(DIC)

accelerated clotting within blood vessels →

increased consumption of platelets and clotting factors →

uncontrollable bleeding

D-dimer general concentrations

500-1000 are seen with trauma, post-sx, liver disease

1000-2000 and above are strongly specific for thromboembolism